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Biologics glossary & taxonomy

Evolving Terminologies for Emerging Technologies
Comments? Questions? Revisions?
Mary Chitty, MSLS
Last revised January 07, 2020

SCOPE NOTE  Biologics include vaccines gene therapies, cell therapies, Immuno-oncology, biosimilars, antibodies, antibody drug conjugates, bispecific antibodies.

Currently, there is no simple way to define all the drugs that are reported to be biologics. There are multiple factions that wish to define biologics in various ways. Some would apply a strict definition of biologics dictating that these products share two critical traits that distinguish their physical makeup from chemically derived drugs: only living systems can produce them, and biologics are relatively large molecules, with an inherently heterogeneous structure that can contain hundreds of amino acids. Some groups would expand the definition of biologics to include any substance composed of organic molecules, no matter how small. Still others feel that any biologically derived product can be called a biologic, and still more think that any complex molecule — no matter how it is manufactured — should be in this class. Others would include substances that are created in other organisms but are not highly complex, such as the estrogen hormones extracted from pregnant mare urine (Premarin). … With a few exceptions, this article will use the definition that biologics are created by either a microorganism or mammalian cell and are large complex molecules, most of which are proteins or polypeptides.  ; Chemical drugs are often more pure and better characterized by current analytical technology than biologics. A biologic agent’s activity may be affected by the cell system in which it is produced, the fermentation media, or operating conditions. 
The use of living organisms to produce therapeutic extracts is not new. What is new is manipulation of these organisms’ genetics to produce specific therapeutics.  Defining the difference: What Makes Biologics Unique Thomas Morrow, MD and Linda Hull-Felcone, Biotechnol Healthc. 2004 Sep; 1(4): 24-26,28-29.

Related glossaries & taxonomiesBiologics overview   Bioprocessing & Manufacturing   Cancer       Drug & Disease targets   Drug discovery & development    Drug  Safety   Stem cells

Adoptive T Cell Therapy Engineering Clinically relevant Therapies  May 6-7, 2020  • Boston, MA | CAR Ts, TCRs and TILs focuses on the latest tools, techniques, and engineering strategies driving the development of cellular immunotherapies for cancer and immune disorders. Focus will be given to clinical progress with Chimeric Antigen Receptors (CAR), T Cell Receptors (TCR), Tumor Infiltrating Lymphocytes (TIL) and Natural Killer (NK) cells, with dedicated sessions on off-the-shelf platforms, solid tumors and lessons learnt from the clinic.

antibody: A protein (immunoglobulin) produced by the immune system of an organism in response to exposure to a foreign molecule (antigen) and characterized by its specific binding to a site of that molecule (antigenic determinant or epitope). IUPAC Compendium

A protein, belonging to the class of immunoglobulins, designed to bind a specific antigen in order to remove it from the body. They are synthesised exclusively by B-lymphocytes, in millions of forms, each with a different amino acid sequence and a specific  for a specific antigen (antigenic determinant or epitope). IUPAC Bioinorganic

Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS), or with an antigen closely related to it.  MeSH   

Narrower terms: domain antibodies, fully human antibodies, hybridoma, monoclonal antibodies, polyclonal antibodies, recombinant antibodies, therapeutic antibodies,. primary antibodies, secondary antibodies   Related terms: epitope, immunogen, immunoglobulin; Assays & screening competitive immunoassay, immunoassay; Microarrays antibody microarray 

Antibody Resource Page,
Monoclonal Antibodies & Therapies
, Nature, 2004 

antibody affinity: A measure of the binding strength between antibody and a simple hapten or antigen determinant. It depends on the closeness of stereochemical fit between antibody combining sites and antigen determinants, on the size of the area of contact between them, and on the distribution of charged and hydrophobic groups. It includes the concept of "avidity," which refers to the strength of the antigen- antibody bond after formation of reversible complexes. MeSH, 1979

Antibody Discovery Forum 2019 Sept 1718 - Boston MA

antibody drug conjugates: Antibody-drug conjugates  (ADCs) are defined as antibodies to which other molecules are bound through a chemical linker. The term “conjugate” differentiates these modified antibody forms from peptide fusions that may be genetically fused to N- or C-termini of either the light or heavy chains of the antibody. The general principle of ADCs is to use the antibody to target a particular cell population, thereby carrying the conjugated molecule to that targeted cell population so that it can exert most, if not all, of its pharmacological activity upon just that population.  Science Direct, Medicine & Chemistry, Antibody Drug Conjugates

Antibody-Drug Conjugates January 21-22 , 2020 • San Diego, CA |  have demonstrated their ability to deliver cytotoxic small-molecule drugs through a selective and targeted mechanism in the fight against cancer. In recent years, ADCs have entered almost 600 clinical trials with more than 60 distinct ADC molecules currently under development. Despite the enormous promise, a low therapeutic index has plagued ADC development, particularly for treating solid tumors..

ANTIBODY DRUG CONJUGATES 2020  May 6-7 BOSTON MA  A successful ADC requires the combination of the right target, right antibody, right linker and the right payload. Getting it right can create ADCs that have the potential to become a life-saving medicine for many diseases, especially cancer.

By tethering a small molecule to a biologic, antibody-drug conjugates are engineered to deliver small molecules to targeted locations using biologic monoclonal antibodies as honing mechanisms. Bristol Myers Squibb: Areas of Focus

Clinical Progress of Antibody-Drug Conjugates Advancing Novel ADC Platforms and Combinations to the Clinic May 4-8 2020  Boston MA  Today, there are about 80 ADCs in clinical development, with 2 to 3 novel ADCs likely to be approved within the next few years. The clear clinical benefit of ADCs is only overshadowed by its dose-limiting toxicities, but recent improvements in technology combined with clinical data from past ADC programs and related fields are helping to shape the next generation of bioconjugates.

Antibody drug conjugates next generation 2019 Nov 18-19 Lisbon Portugal As more Antibody-Drug Conjugates head to market, the next-generation of ADCs looms on the horizon. Next-gen engineering requires designing an optimal antibody, payload, linker and conjugation method while ensuring stability, targeted delivery, and limited off-target effects.

ANTIBODY ENGINEERING: New Science and Technologies for the Selection, Engineering and Targeting of Next Generation Therapeutic Antibodies and Biotherapeutics  May 6-7 2020 Boston MA  The field of protein engineering is at an exciting point in its development, with new generations of therapeutic antibodies now progressing through development and into the market, great advances in protein science and discovery technology and a body of clinical evidence that can be used to inform the development of safe, highly effective therapies for unmet medical needs

NFCR Center for Therapeutic Antibody Engineering, National Foundation for Cancer Research 

antibody therapeutics: Related terms: monoclonal antibodies, protein therapeutics 

antigen: A compound (protein, polysaccharide, microorganism, virus) foreign to the body that induces the production of specific antibodies. IUPAC Bioinorganic  Related terms antibody, epitope

antisense therapy:  a form of treatment for genetic disorders or infections. When the genetic sequence of a particular gene is known to be causative of a particular disease, it is possible to synthesize a strand of nucleic acid (DNARNA or a chemical analogue) that will bind to the messenger RNA (mRNA) produced by that gene and inactivate it, effectively turning that gene "off". …This synthesized nucleic acid is termed an "anti- sense"   oligonucleotide (AON) because its base sequence is complementary to the gene's messenger RNA (mRNA), which is called the "sense" sequence…Antisense oligonucleotides have been researched as potential drugs[2][3][4] for diseases such as cancers (including lung cancercolorectal carcinomapancreatic carcinoma, malignant glioma and malignant melanoma), diabetesamyotrophic lateral sclerosis (ALS), Duchenne muscular dystrophyspinal muscular atrophy, Ataxia-telangiectasia (in vitro) and diseases such as  asthma arthritis  and pouchitis with an inflammatory component. As of 2016, several antisense drugs have been approved by the U.S. Food and Drug Administration (FDA):   Wikipedia accessed 2019 Jan 21    See also Pharmaceutical biology antisense

biogenerics: Regulatory  See also biosimilars

biological pharmacokinetics: Monoclonal antibodies (MAbs) exhibit complex pharmacokinetics (PK) and pharmacodynamics (PD, response) against tumor necrosis factor (TNF). Many factors impact anti-TNF MAb PK, altering MAb clearance and therefore the half-life: albumin, weight (particularly, obesity), disease (severity, stage and co-morbidities) and concomitant administration of immunosuppressants (e.g. methotrexate). These factors can alter MAb exposure, impacting on the likelihood of clinical response. Formation of anti-drug antibodies (ADAs) is another potential factor that can affect MAb PK. Factors impacting the likelihood of developing ADA are classified as patient-related (concomitant immunosuppressants, prior ADA against other anti-TNF MAb) or product-related (structure, manufacturing process, aggregate formation, route of administration and dosing regimen). Mould D, R: The Pharmacokinetics of Biologics: A Primer. Dig Dis 2015;33(suppl 1):61-69. doi: 10.1159/000437077

biological product: Virus, therapeutic serum, toxin, antitoxin, or analogous product applicable to the prevention, treatment, or cure of diseases or injuries in humans and/or animals. Note: The term “analogous product” may include essentially all biotechnology-derived products and procedures including gene therapy, transgenics, and somatic cell therapy.   IUPAC Pharmaceutics

biologic(s): Biologics, in contrast to drugs that are chemically synthesized, are derived from living sources (such as humans, animals, and microorganisms). Most biologics are complex mixtures that are not easily identified or characterized, and many biologics are manufactured using biotechnology. Biological products often represent the cutting- edge of biomedical research and, in time, may offer the most effective means to treat a variety of medical illnesses and conditions that presently have no other treatments available.  About CBER, FDA, US 

Veterinary biologics (vaccines, bacterins, diagnostics, etc., which are used to prevent, treat, or diagnose animal diseases) are regulated by the U.S. Department of Agriculture.

Any virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic products, or analogous product applicable to the prevention, treatment, or cure of diseases or injuries in man.  Includes blood, vaccines, tissue, allergenics and biological therapeutics.

biopharmaceutical:  also known as a biologic(al) medical productbiological,[1] or biologic, is any pharmaceutical drug product manufactured in, extracted from, or semisynthesized from biological sources. Different from totally synthesized pharmaceuticals, they include vaccinesblood, blood components, allergenicssomatic cellsgene therapiestissuesrecombinant therapeutic protein, and living cells used in cell therapy. Biologics can be composed of sugars, proteins, or nucleic acids or complex combinations of these substances, or may be living cells or tissues. They (or their precursors or components) are isolated from living sources—human, animal, plant, fungal, or microbial.

Terminology surrounding biopharmaceuticals varies between groups and entities, with different terms referring to different subsets of therapeutics within the general biopharmaceutical category. Some regulatory agencies use the terms biological medicinal products or therapeutic biological product to refer specifically to engineered macromolecular products like protein- and nucleic acid-based drugs, distinguishing them from products like blood, blood components, or vaccines, which are usually extracted directly from a biological source.[2][3][4] Specialty drugs, a recent classification of pharmaceuticals, are high-cost drugs that are often biologics.[5][6][7] The European Medicines Agency uses the term advanced therapy medicinal products (ATMPs) for medicines for human use that are "based on genes, cells, or tissue engineering",[8] including gene therapy medicines, somatic-cell therapy medicines, tissue-engineered medicines, and combinations thereof.[9] Within EMA contexts, the term advanced therapies refers specifically to ATMPs, although that term is rather nonspecific outside those contexts. Wikipedia accessed 2018 March 1

bispecific antibodies:  A type of antibody that can bind to two different antigens at the same time. Bispecific antibodies are being studied in the imaging and treatment of cancer. They are made in the laboratory. National Cancer Institute, NCI Dictionary of Cancer Terms

Creating bioactive molecules that are multivalent and multifunctional offers the promise of more effective therapeutics. By binding to at least two molecular targets simultaneously, antibodies are empowered, thereby delivering a highly potent therapeutic, particularly for cancer immunotherapy.   Broader term: multispecific antibodies   

Bispecific Antibody Therapeutics

Engineering Bispecific Antibodies Improving Therapeutic Properties for Oncology and Beyond  May 7-8 2020 • Boston, MA |  The universe of bispecific antibody platforms, combinations, strategies and chemistry is growing exponentially and the application of bispecific constructs in immunotherapy is proving to be an extremely effective combination. Fine tuning specificity, calibrating potency while minimizing safety risk are all top priorities of antibody engineers for targets in oncology, immuno-oncology and infectious disease. Early results with new platforms and evolving techniques will be shared.

Bispecific Antibody Pipeline Congress  August 24-27, 2020 Washington DC  key opinion leaders including regulators, clinicians, and industry experts to deepen our understanding of bispecific therapeutics and exchange innovative ideas to foster meaningful research collaborations.

Bispecific Antibody Therapeutics January 23-24, 2020, San Diego explores the challenges of engineering multi-specificity to achieve more effective therapies that bind to at least two molecular targets simultaneously. These next-generation antibody formats are showing efficacy in the efforts to conquer cancer and other diseases. Case studies will highlight novel engineering approaches that address safety, stability, enhanced targeting, and manufacturability.

Bispecific engineering 2019 Nov 21-22 Lisbon Portugal therapeutics that have optimal stability and half-life, and proven functionality. Balancing the affinity of the two arms of the bispecific, especially for CD3 targeting products, is seen as a common challenge and efforts are clearly underway to overcome this for enhanced targeting and minimal toxicity.

Bispecifics & combination therapy: Advancing Bispecifics and Combination Therapy to the Clinic 2019 Nov 21-22 Lisbon Portugal features case studies for haematological and solid tumours, bispecific-like products and biotherapeutics in combination. Presenters explain the rationale for the choice of combination, the background to the mode of action and how the products perform, as well as PK profile, PK/PD relationships, safety/toxicology studies, getting the right potency: side effect balance, translational studies, and risk assessment. Where appropriate, investigators present clinical trial design, demonstration of safety, issues that have arisen and have been resolved, proof of concept, dose escalation studies, and interaction with clinicians.

biotechnology: The integration of natural sciences and engineering sciences in order to achieve the application of organisms, cells, parts thereof  and molecular analogues for products and services. IUPAC Compendium

It is important to understand the distinction between biotechnology as a new process technology and as a drug discovery research tool. The first uses genetic engineering to manufacture large molecular weight drugs that cannot be directly synthesized or extracted. The second involves understanding the molecular basis of disease and the search for new therapeutic targets  using techniques such as cloned receptors as screens or transgenic organisms created through gene knock-out technologies to determine protein function; most of the focus is on small molecule drugs that interact against those targets. As the pharmaceutical industry is using biotechnology in drug discovery, it will likely maintain its dominant position in small molecules, but the development and manufacture of protein based therapeutics requires a completely different set of core competencies. Product Definition, The Biopharmaceutical Sector, Industry Canada, 2003      Related terms: Business biotechnology firms, biotechnology industry 

CAR T, TIL and TCT therapy 2019 Nov 20-21 Lisbon Portugal The stunning success of CAR T therapy over the past couple of years has spawned a new industry and a proliferation of CAR, TCR and TIL constructs. Engineering efforts are aimed at improving the design, targeting, developability, manufacturing, and scalability of new formats to solve issues that remain, including improving the safety of immunotherapy, affordability and targeting of solid tumors. The tumor microenvironment and the microbiome are being tapped to predict the efficacy of immunotherapy and optimize results.

CAR Ts, TCRs and TILs Latest Innovations and Developments in Adoptive Cell Therapy May 6-7 2020 Boston MA  CAR Ts, TCRs and TILs focuses on the latest tools, techniques, and engineering strategies driving the development of cellular immunotherapies for cancer and immune disorders. Focus will be given to clinical progress with Chimeric Antigen Receptors (CAR), T Cell Receptors (TCR), Tumor Infiltrating Lymphocytes (TIL) and Natural Killer (NK) cells, with dedicated sessions on off-the-shelf platforms, solid tumors and lessons learnt from the clinic.

See also Chimeric Antigen Receptors CARs

cell based therapies: Cell therapy represents the most recent phase of the biotechnology revolution in medicine. As with many remedies, cell therapies are based on ground-breaking scientific discoveries and technology advancements. Most cell-based therapies are currently experimental, with a few exceptions such as haematopoietic stem cell (HSC) transplantation which is already a well-established treatment for blood related disorders [1,2]. The next generation of cell therapies now emerging are of diverse class. Cell therapies can be classified by the therapeutic indication they aim to address, e.g. neurological, cardiovascular, ophthalmological; by whether they comprise cells taken from and administered to the same individual (autologous) or derived from a donor (allogeneic); or most commonly by the cell types, often using the EU regulatory classification. The EU regulatory classification of cell-based therapies discriminates between minimally manipulated cells for homologous use (transplants or transfusions) and those regulated as medicines which are required to demonstrate quality, safety and efficacy standards to obtain a marketing authorization before becoming commercially available (referred to as Advanced Therapy Medicinal Products; ATMPs) which are further subdivided into somatic cell, gene therapy and tissue engineered products. Another way of considering the diversity of cell therapies is classification by their underlying technology. Broadly, the ATMP subdivisions are mirrored in the cell-therapy technology classification described in this paper. The technology, i.e. methodology, being used, rather than the specific cell type is often the feature that needs to be addressed to solve manufacturing, regulatory and clinical issues in a more general way. Thus, a technology classification can emphasize the commonality in translation challenges between otherwise diverse types of cell-based therapy. Mount NM, Ward SJ, Kefalas P, Hyllner J. Cell-based therapy technology classifications and translational challenges. Philos Trans R Soc Lond B Biol Sci. 2015;370(1680):20150017.

Chimeric antigen receptors (CARs, also known as chimeric immunoreceptorschimeric T cell receptors or artificial T cell receptors) are engineered receptors that combine a new specificity with an immune cell to target cancer cells. Typically, these receptors graft the specificity of a monoclonal antibody onto a T cell. The receptors are called chimeric because they are fused of parts from different sources. CAR-T cell therapy refers to a treatment that uses such transformed cells for cancer therapy. Wikipedia accessed 2018 Aug 22

cellular therapy:  Cellular therapy products include cellular immunotherapies, cancer vaccines, and other types of both autologous and allogeneic cells for certain therapeutic indications, including hematopoetic stem cells and adult and embryonic stem cells.  FDA, Cellular & Gene Therapy products  
Related terms: gene therapy, myoblasts, stem cells; Cancer  cancer vaccines
See also high content analysis  Stem cells

Chimeric Antigen Receptors (CAR): Recombinant receptors that provide both antigen-binding and T-cell-activating functions. A multitude of CARs has been reported over the past decade, targeting an array of cell surface tumor antigens. … CARs are a new class of drugs with great potential for cancer immunotherapy. Upon their expression in T lymphocytes, CARs direct potent, targeted immune responses that have recently shown encouraging clinical outcomes in a subset of patients with B-cell malignancies. The basic principles of chimeric antigen receptor design. Sadelain M, Brentiens R, Riviere I, Cancer Discov. 2013 Apr; 3 (4): 388-398. doi: 10.1158/2159-8290.CD-12-0548. Epub 2013 Apr 2.

Receptors, Chimeric Antigen: Synthetic cellular receptors that reprogram T-LYMPHOCYTES to selectively bind antigens. MeSH 2019

combination products: Regulatory

developability biologics: Monoclonal antibodies constitute a robust class of therapeutic proteins. Their stability, resistance to stress conditions and high solubility have allowed the successful development and commercialization of over 40 antibody-based drugs. Although mAbs enjoy a relatively high probability of success compared with other therapeutic proteins, examples of projects that are suspended due to the instability of the molecule are not uncommon. Developability assessment studies have therefore been devised to identify early during process development problems associated with stability, solubility that is insufficient to meet expected dosing or sensitivity to stress. This set of experiments includes short-term stability studies at 2-8 þC, 25 þC and 40 þC, freeze-thaw studies, limited forced degradation studies and determination of the viscosity of high concentration samples.  Yang X, Xu W, Dukleska S, et al. Developability studies before initiation of process development: Improving manufacturability of monoclonal antibodies. mAbs. 2013;5(5):787-794. doi:10.4161/mabs.25269.  See also Drug discovery & Development developability

DNA vaccines: Recombinant DNA vectors encoding antigens administered for the prevention or treatment of disease. The host cells take up the DNA, express the antigen, and present it to the immune system in a manner similar to that which would occur during natural infection. This induces humoral and cellular immune responses against the encoded antigens. The vector is called naked DNA  because there is no need for complex formulations or delivery agents; the plasmid is injected in saline or other buffers. MeSH, 1997    Broader term: vaccines 

domain antibodies:  The smallest known antigen- binding fragments of antibodies, ranging from 11 kDa to 15 kDa. ... owing to their small size and inherent stability, can be formatted into larger molecules to create drugs with prolonged serum half- lives or other pharmacological activities. LJ Holt et. al, Domain Antibodies: Proteins for Therapy, Trends in Biotechnology, 21 (11): 484- 490, Nov. 2003

formulation biologics: Drug delivery

fusion protein therapeutics: Engineering for Clinical Success APRIL 8-9, 2019 Boston MA  Chimeric fusion proteins, with their ability to extend plasma half-life and prolong therapeutic activity, offer exciting benefits over antibody-based therapeutics. Companies are intensely investigating into fusion protein therapeutics as a promising alternative to antibodies. See also recombinant proteins

gene therapy: Human gene therapy is the administration of genetic material to modify or manipulate the expression of a gene product or to alter the biological properties of living cells for therapeutic use 1. Gene therapy is a technique that modifies a person’s genes to treat or cure disease. Gene therapies can work by several mechanisms,: Replacing a disease-causing gene with a healthy copy of the gene, Inactivating a disease-causing gene that is not functioning properly, Introducing a new or modified gene into the body to help treat a disease. Gene therapy products are being studied to treat diseases including cancer, genetic diseases, and infectious diseases. There are a variety of types of gene therapy products, including: Plasmid DNA: Circular DNA molecules can be genetically engineered to carry therapeutic genes into human cells., Viral vectors: Viruses have a natural ability to deliver genetic material into cells, and therefore some gene therapy products are derived from viruses. Once viruses have been modified to remove their ability to cause infectious disease, these modified viruses can be used as vectors (vehicles) to carry therapeutic genes into human cells. Bacterial vectors: Bacteria can be modified to prevent them from causing infectious disease and then used as vectors (vehicles) to carry therapeutic genes into human tissues. Human gene editing technology: The goals of gene editing are to disrupt harmful genes or to repair mutated genes. Patient-derived cellular gene therapy products: Cells are removed from the patient, genetically modified (often using a viral vector) and then returned to the patient.

The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. MeSH, 1989

Gene Therapy covers both the research and clinical applications of the new genetic therapy techniques currently being developed. Over the last decade, gene therapy protocols have entered clinical trials in increasing numbers and as they cover a wide spectrum of diseases, these studies promise to unite the diverse organ-based specialties into which modern medicine has become divided. Gene Therapy covers all aspects of gene therapy as applied to human disease, including: novel technological developments for gene transfer, control and silencing, basic science studies of mechanisms of gene transfer and control of expression, preclinical animal model systems and validation studies, clinical trial reports which have significant impact for the field, gene-based vaccine development and applications, cell-based therapies including all aspects of stem cells and genetically modified cellular approaches. Aims and Scope, Gene Therapy, Nature

The term 'gene therapy' encompasses at least four types of application of genetic engineering for the insertion of genes into humans. The scientific requirements and the ethical issues associated with each type are discussed. Somatic cell gene therapy is technically the simplest and ethically the least controversial. The first clinical trials will probably be undertaken within the next year [1986]. Germ line gene therapy will require major advances in our present knowledge and it raises ethical issues that are now being debated. In order to provide guidelines for determining when germ line gene therapy would be ethical, the author presents three criteria which should be satisfied prior to the time that a clinical protocol is attempted in humans. Enhancement genetic engineering presents significant, and troubling, ethical concerns. Except where this type of therapy can be justified on the grounds of preventive medicine, enhancement engineering should not be performed. The fourth type, eugenic genetic engineering, is impossible at present and will probably remain so for the foreseeable future, despite the widespread media attention it has received. W. French Anderson "Human gene therapy: scientific and ethical considerations" J Med Philosophy 10 (3): 275- 291, Aug. 1985  

Cellular & gene therapy, 
Related terms: human gene transfer, genetic enhancement; DNA glossary: recombinant DNA  Molecular diagnostics: 
especially preimplantation diagnosis

genetic immunization: The concept and demonstration of genetic immunization (GI) was first introduced in 1992. At the time it appeared to be a revolutionary new approach in vaccinology. Since then, genetic immunization has been applied with much success in a wide variety of model and natural systems. It has also been used in several human clinical trials. Currently there is a general impression that genetic immunization has limitations inhibiting its broad use. The technique is thought to be poor at antibody production and more importantly not to work well in primates and humans (simian barrier). However, recent reports addressing these issues (poor antibody production and the simian barrier) showed improvements of GI to produce protective immune responses in humans. We propose that the apparent limitations of gene vaccines may arise from not using the technologies' potential to manipulate the immune system. This dearth of imaginative use is manifested in the tendency by some to term the technique DNA immunization. The apparent limitations of DNA vaccines may not be limitations for gene vaccines. Genetic Immunization Johnston, Stephen Albert et al Archives of Medical Research , Volume 33 , Issue 4 , 325 – 329  Related terms: DNA vaccines,  gene therapy

humanized antibodies; antibodies from non-human species whose protein sequences have been modified to increase their similarity to antibody variants produced naturally in humans.[1][2] The process of "humanization" is usually applied to monoclonal antibodies developed for administration to humans (for example, antibodies developed as anti-cancer drugs). Humanization can be necessary when the process of developing a specific antibody involves generation in a non-human immune system (such as that in mice). The protein sequences of antibodies produced in this way are partially distinct from homologous antibodies occurring naturally in humans, and  are therefore potentially  immunogenicwhen administered to human patients  … Humanized antibodies are distinct from chimeric antibodies. The latter also have their protein sequences made more similar to human antibodies, but carry a larger stretch of non-human protein.. Wikipedia accessed 2018 Nov 18

immunocytokines: antibody-cytokine fusion proteins, with the potential to preferentially localize on tumor lesions and to activate anticancer immunity at the site of disease. Various tumor targets (e.g., cell membrane antigens and extracellular matrix components) and antibody formats (e.g., intact IgG and antibody fragments) have been considered for immunocytokine development and some products have advanced to clinical trials.  Neri D, Sondel PM. Immunocytokines for cancer treatment: past, present and future. Curr Opin Immunol. 2016;40:96-102.

immunotechnology:  Technology based on applications of cells and molecules of the immune system. A major research interest is the application of human recombinant antibodies and antibody fragments in medical and industrial applications, as well as studies of mechanisms underlying somatic mutations in B cells and IgE switch in allergy. The use of synthetic antibodies in proteome analysis, including protein array technology is also pursued as well as gene array analysis of the transcriptome. B cell malignancies is one focus in antibody and gene therapy projects as well as viral infection in molecular breeding projects. Dept. of Immunotechnology, Lund Univ., Sweden  

Refers to any approach aimed at mobilizing or manipulating a patient's immune system to treat or cure disease. Although the term has been most often associated with therapies for established malignancies, immunotherapy is of increasing interest as an approach to arrest cancer at a much earlier stage. In addition as illustrated in the accompanying articles, immunotherapy is pertinent to the investigation and treatment of transplantation, autoimmunity, chronic inflammation, and infectious disease. Ralph M Steinman and Ira Mellman, Immunotherapy; Bewitched, Bothered and Bewildered No more. Science 305: 197- 200, 9 July 2004

The concept of using the immune system to treat disease, for example, developing a vaccine against cancer. Immunotherapy may also refer to the therapy of diseases caused by the immune system, allergies for example. NHGRI

Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. MeSH, 1973 

immunotoxins:  Semi-synthetic conjugates of various toxic molecules, including radioactive isotopes and bacterial or plant toxins, with specific immune substances such as immunoglobulins, monoclonal antibodies, and antigens. The antitumor or antiviral immune substance carries the toxin to the tumor or infected cell where the toxin exerts its poisonous effect. MeSH, 1990 Broader term: antibodies

Lead and candidate selection for Therapeutic proteins JANUARY 21-22, 2020, San Diego CA  The screenings and studies that comprise a company's lead and candidate selection funnel are an essential stage of biopharmaceutical R&D. Good selections not only ensure that the best quality molecules are chosen for advancement, but that these match target profile for efficacy, safety, and pharmacology.

ligand: Pharmaceutical biology  ligand binding assays: Assays 

monoclonal antibodies: A single species of immunoglobulin molecules produced by culturing a single clone of a hybridoma cell. MAbs recognize only one chemical structure, i.e., they are directed against a single epitope of the antigenic substance used to raise the antibody. IUPAC Biotech

Antibodies produced by clones of cells such as those isolated after hybridization of activated B lymphocytes with neoplastic cells. These hybrids are often referred to as hybridomas. MeSH, 1982  Broader term: antibody; Related terms: clinical antibodies, cloning, hybridoma, fully humanized antibodies, polyclonal antibodies,  recombinant antibodies,  therapeutic antibodies, polyclonal antibodies 

Development of Therapeutic Monoclonal Antibody Products A Comprehensive Guide to CMC Activities from Clone to Clinic  Insight Pharma Reports 2017 As the pharmaceutical market in the United States and the rest of the world continues to expand, biopharmaceutical products have taken on increasing importance in the treatment of disease. Sales of monoclonal antibody products have grown from approximately $50 billion in 2010 to almost $90 billion in 2015, an approximately 1.8‑fold increase and represent approximately 58% of biopharmaceutical sales.  As more and more exciting monoclonal antibody products for treatment of cancer, autoimmune diseases, cardiovascular disease, and others are introduced, sales from new products approved in the coming years will drive the world-wide sales of monoclonal antibody products to approximately $110 billion by 2018 and nearly $150 billion by 2021.

multispecific antibodies: A classical antibody’s two arms will bind specifically to one antigen. Expertise in molecular design has led to novel antibody formats with additional features. One approach implies engineering multiple antigen binding domains into a single antibody molecule. These so-called bi-or multispecific antibodies combine two or more antigen-recognising elements into a single molecule, able to bind to two or more targets. Roche R*D  Narrower term: Bispecific antibodies

next generation antibodies: New opportunities for antibody drugs may be possible by developing antibodies with novel mechanisms of action, such as those that induce tumour cell killing or receptor agonism.  Additional opportunities for antibody drugs are anticipated by overcoming existing obstacles to delivery, such as poorly accessible sites of action including the brain, lungs and gastrointestinal tract and perhaps ultimately the cytosol of cells. Bispecific and multispecific targeting with antibodies is enabling advances in immune cell recruitment, improvements in tissue selectivity and novel mechanistic approaches to agonism and transport. Targets that are currently not amenable to antibody approaches — the 'high-hanging fruit' — may become druggable in the future through continued innovation. Next generation antibody drugs: pursuit of the 'high-hanging fruit' Paul J. Carter  & Greg A. Lazar Nature Reviews Drug Discovery volume17, pages197–223 (2018)

Oligonucleotide & Precision Therapeutics  March 17-18, 2020 Cambridge, MA reveals the latest strategies at the forefront of discovery, chemistry and delivery with in-depth sessions on new chemistries, novel delivery mechanisms and the most important preclinical and clinical advances. Leading oligonucleotide scientists deliver detailed case studies on antisense, RNA, aptamers and conjugates .

Oligonucleotide Discovery & Delivery  March 17-18, 2020 Cambridge, MA   | detailed case studies on antisense, RNA, aptamer and oligonucleotide conjugates  .

oligonucleotide therapeutics: In this review we address the development of oligonucleotide (ON) medicines from a historical perspective by listing the landmark discoveries in this field. The various biological processes that have been targeted and the corresponding ON interventions found in the literature are discussed together with brief updates on some of the more recent developments. Most ON therapies act through antisense mechanisms and are directed against various RNA species, as exemplified by gapmers, steric block ONs, antagomirs, small interfering RNAs (siRNAs), micro-RNA mimics, and splice switching ONs. However, ONs binding to Toll-like receptors and those forming aptamers have completely different modes of action. Similar to other novel medicines, the path to success has been lined with numerous failures, where different therapeutic ONs did not stand the test of time. Since the first ON drug was approved for clinical use in 1998, the therapeutic landscape has changed considerably, but many challenges remain until the expectations for this new form of medicine are met. However, there is room for cautious optimism. Oligonucleotide Therapies: The Past and the Present  Karin E. Lundin,* Olof Gissberg, and C.I. Edvard Smith Hum Gene Ther. 2015 Aug 1; 26(8): 475–485.Published online 2015 Jul 8. doi:  10.1089/hum.2015.070

PEGS: the essential protein engineering summit	PEGS: the essential protein engineering summit  May 4-8, 2020 • Boston, MA  | Conference programs include protein and antibody engineering, cancer immunotherapy, oncology, and emerging therapeutics.

PEGS EuropePEGS Europe  2019 Nov 18-22 Lisbon Portugal Conference programs include Engineering, Oncology, Analytical, Immunotherapy, Expression and Bispecifics.


PepTalk  January 20-24, 2020 • San Diego, CA | 
Conference programs include Protein Engineering and Development, Innovations in Discovery and Development, Antibody Therapeutics,  Formulation and Stability, Analytics & Impurities, Process Technologies & Purification, Biotherapeutic expression & production, Alternative expression & products.

peptide therapeutics: Peptide therapeutics have played a notable role in medical practice since the advent of insulin therapy in the 1920s. Over 60 peptide drugs are approved in the United States and other major markets, and peptides continue to enter clinical development at a steady pace. Peptide drug discovery has diversified beyond its traditional focus on endogenous human peptides to include a broader range of structures identified from other natural sources or through medicinal chemistry efforts.  Therapeutic peptides: Historical perspectives, current development trends, and future directions, Jolene L.Lau, Michael K.Dunn  Bioorganic & Medicinal Chemistry  2017

polyclonal antibodies:   

primary and secondary antibodies: two groups of antibodies that are classified based on whether they bind to antigens or proteins directly or target another (primary) antibody that, in turn, is bound to an antigen or protein. … A primary antibody can be very useful for the detection of biomarkers for diseases such as cancer, diabetes, Parkinson’s and Alzheimer’s disease and they are used for the study of absorption, distribution, metabolism, and excretion (ADME) and multi-drug resistance (MDR) of therapeutic agents. Secondary antibodies can be conjugated to enzymes such as horseradish peroxidase (HRP) or alkaline phosphatase (AP); or fluorescent dyes such as fluorescein isothiocyanate  (FITC), rhodamine derivatives, Alexa Fluor dyes; or other molecules to be used in various applications. Secondary antibodies are used in many biochemical assays [2] including: ELISA, including many HIV tests, Western blot, Immunostaining, Immunohistochemistry, Immunocytochemistry  Wikipedia

protein therapeutics: Once a rarely used subset of medical treatments, protein therapeutics have increased dramatically in number and frequency of use since the introduction of the first recombinant protein therapeutic — human insulin — 25 years ago. Protein therapeutics already have a significant role in almost every field of medicine, but this role is still only in its infancy. Protein therapeutics: a summary and pharmacological classification, Benjamin Leader, Quentin J. Baca & David E. Golan Nature Reviews Drug Discovery 7, 21-39 (January 2008) | doi:10.1038/nrd2399  

Although small molecules (which allow oral delivery) are preferred  for drugs, a number of therapeutic proteins are available, and the number has increased with progress in biotechnology and genetic engineering.  Important commercial products include insulin, monoclonal antibodies,  growth factors, and various blood and plasma proteins. Related terms:  antibody therapeutics, peptide therapeutics, protein aggregation

recombinant antibodies: As new recombinant DNA technology continues to join with cellular and molecular immunology, the field of antibody engineering has become a flourishing discipline. Antibody genes are now being cloned, genetically manipulated, and expressed to produce antigen binding proteins. Recombinant Antibodies, Wiley 1999 

Recombinant Protein Therapeutics Fusion proteins and beyond January 20-21, 2020 • San Diego, CA |  focuses on the varying designs of fusion protein-based therapeutics and the latest data from R&D to post-approval, including Case Studies. By combining modular building blocks that can reach targets not accessible to antibodies, Fusion Protein Therapies possess advantages over antibody-based therapies; their customizable functionality translates into lower patient dosing, reduced production costs, and improved product homogeneity. This conference will demonstrate how these molecules are being engineered to form more efficacious therapeutics that offer specificity with enhanced stability and longer half-life.  See also fusion proteins.

recombination : The formation of new combinations and arrangements of genes during meiosis; recombination is achieved by crossing over, independent assortment, and segregation. NHLBI  Can be natural or synthetic. Narrower terms:  genetic recombination,  recombinant antibodies, recombinant proteins  

reverse vaccinology: Today, the possibility of using genomic information allows us to study vaccine development in silico, without the need of cultivating the pathogen. This approach, which we have named 'reverse vaccinology', reduces the time required for the identification of candidate vaccines and provides new solutions for those vaccines which have been difficult or impossible to develop. Rappuoli R. Reverse vaccinology, a genome- based approach to vaccine development, Vaccine. 19 (17-19) 2688- 2691, Mar 21, 2001 

The basic idea behind reverse vaccinology is that an entire pathogenic genome can be screened using bioinformatics approaches to find genes. Some of the traits that the genes are monitored for that may indicate antigenicity include genes that code for proteins with extracellular localization, signal peptides, and B-cell epitopes.[3] Next, those genes are filtered for desirable attributes that would make good vaccine targets such as outer membrane proteins. Once the candidates are identified, they are produced synthetically and are screened in animal models of the infection.[4] Wikipedia accessed 2018 Nov 8 

therapeutic antibodies Emerging Indications for Therapeutic Antibodies R&D ADVANCES IN NON-CANCER INDICATIONS FOR ANTIBODIES AND OTHER BIOTHERAPEUTICS May 4-5,2020, Boston MA  Significant scientific advances in the fields of immunology and protein science are driving the development of biotherapeutic drugs in a growing range of therapeutic areas beyond oncology. These advances are driving the identification of new and unique targets, new approaches to developing biotherapeutics for unserved medical needs, methods of binding to illusive targets and translational science for patient stratification and drug development for niche indications.

vaccine: An agent containing antigens produced from killed, attenuated or live pathogenic microorganisms, synthetic peptides or by recombinant organisms, used for stimulating the immune system of the recipient to produce specific antibodies providing active immunity and/or passive immunity in the progeny. IUPAC Compendium

Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa, or rickettsiae), antigenic proteins derived from them, or synthetic constructs, administered for the prevention, amelioration, or treatment of infectious and other diseases. MeSH  Narrower terms: allogeneic polyvalent vaccines,  allogenic vaccines, autologous vaccines,  DNA vaccine; Related terms: reverse vaccinology;  -Omes & -omics: vaccinome, vaccinomics

vaccine ontology:

veterinary biologics:  vaccines, bacterins, diagnostics, etc. which are used to prevent, treat, or diagnose animal diseases.  These products generally work through some immunological method or process.  Common questions about veterinary biologics USDA, APHIS Common questions about veterinary biologics 2015

Biologics Resources
Centers for Disease Control,
Vaccines acronyms and abbreviations
FDA, Cellular and Gene Therapy Guidances
HHS, Vaccines Glossary
IUPAC  International Union of Pure and Applied Chemistry, Compendium of Chemical Terminology: Recommendations, compiled by Alan D. McNaught and Andrew Wilkinson, Blackwell Science, 1997. "Gold Book"
IUPAC, Glossary of terms related to pharmaceutics, Pure and Applied Chemistry 81, 971–999, 2009

Nature Nature Biologics: latest research and review

NFCR Center for Therapeutic Antibody Engineering Glossary, National Foundation for Cancer Research, Dana Farber Cancer Institute 

Biological Therapeutics Conferences 
PepTalk The Protein Science Week
Protein Engineering Summit PEGS
PEGs Europe

How to look for other unfamiliar  terms

IUPAC definitions are reprinted with the permission of the International Union of Pure and Applied Chemistry.

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