Monoclonal antibody

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A general representation of the method used to produce monoclonal antibodies Monoclonals.png
A general representation of the method used to produce monoclonal antibodies

A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell.

Contents

Monoclonal antibodies can have monovalent affinity, binding only to the same epitope (the part of an antigen that is recognized by the antibody). [3] In contrast, polyclonal antibodies bind to multiple epitopes and are usually made by several different antibody-secreting plasma cell lineages. Bispecific monoclonal antibodies can also be engineered, by increasing the therapeutic targets of one monoclonal antibody to two epitopes.

It is possible to produce monoclonal antibodies that specifically bind to almost any suitable substance; they can then serve to detect or purify it. This capability has become an investigative tool in biochemistry, molecular biology, and medicine. Monoclonal antibodies are used in the diagnosis of illnesses such as cancer and infections [4] and are used therapeutically in the treatment of e.g. cancer and inflammatory diseases.

History

In the early 1900s, immunologist Paul Ehrlich proposed the idea of a Zauberkugel – "magic bullet", conceived of as a compound which selectively targeted a disease-causing organism, and could deliver a toxin for that organism. This underpinned the concept of monoclonal antibodies and monoclonal drug conjugates. Ehrlich and Élie Metchnikoff received the 1908 Nobel Prize for Physiology or Medicine for providing the theoretical basis for immunology.

By the 1970s, lymphocytes producing a single antibody were known, in the form of multiple myeloma – a cancer affecting B-cells. These abnormal antibodies or paraproteins were used to study the structure of antibodies, but it was not yet possible to produce identical antibodies specific to a given antigen. [5] : 324  In 1973, Jerrold Schwaber described the production of monoclonal antibodies using human–mouse hybrid cells. [6] This work remains widely cited among those using human-derived hybridomas. [7] In 1975, Georges Köhler and César Milstein succeeded in making fusions of myeloma cell lines with B cells to create hybridomas that could produce antibodies, specific to known antigens and that were immortalized. [8] They and Niels Kaj Jerne shared the Nobel Prize in Physiology or Medicine in 1984 for the discovery. [8]

In 1988, Gregory Winter and his team pioneered the techniques to humanize monoclonal antibodies, [9] eliminating the reactions that many monoclonal antibodies caused in some patients. By the 1990s research was making progress in using monoclonal antibodies therapeutically, and in 2018, James P. Allison and Tasuku Honjo received the Nobel Prize in Physiology or Medicine for their discovery of cancer therapy by inhibition of negative immune regulation, using monoclonal antibodies that prevent inhibitory linkages. [10]

The translational work needed to implement these ideas is credited to Lee Nadler. As explained in an NIH article, "He was the first to discover monoclonal antibodies directed against human B-cell–specific antigens and, in fact, all the known human B-cell–specific antigens were discovered in his laboratory. He is a true translational investigator, since he used these monoclonal antibodies to classify human B-cell leukemia and lymphomas as well as to create therapeutic agents for patients. . . More importantly, he was the first in the world to administer a monoclonal antibody to a human (a patient with B-cell lymphoma)." [11]

Production

Looking at slides of cultures of cells that make monoclonal antibodies Monoclonal antibodies3.jpg
Looking at slides of cultures of cells that make monoclonal antibodies
Monoclonal antibodies can be grown in unlimited quantities in flasks. Monoclonal antibodies4.jpg
Monoclonal antibodies can be grown in unlimited quantities in flasks.
Hand-filling wells with a liquid for a research test. This test involves preparation of cultures in which hybrids are grown in large quantities to produce desired antibody. This is effected by fusing a myeloma cell and a mouse lymphocyte to form a hybrid cell (hybridoma). Monoclonal antibodies1.jpg
Hand-filling wells with a liquid for a research test. This test involves preparation of cultures in which hybrids are grown in large quantities to produce desired antibody. This is effected by fusing a myeloma cell and a mouse lymphocyte to form a hybrid cell (hybridoma).
Bathing prepared slides in a solution Monoclonal antibodies2.jpg
Bathing prepared slides in a solution

Hybridoma development

Much of the work behind production of monoclonal antibodies is rooted in the production of hybridomas, which involves identifying antigen-specific plasma/plasmablast cells that produce antibodies specific to an antigen of interest and fusing these cells with myeloma cells. [8] Rabbit B-cells can be used to form a rabbit hybridoma. [12] [13] Polyethylene glycol is used to fuse adjacent plasma membranes, [14] but the success rate is low, so a selective medium in which only fused cells can grow is used. This is possible because myeloma cells have lost the ability to synthesize hypoxanthine-guanine-phosphoribosyl transferase (HGPRT), an enzyme necessary for the salvage synthesis of nucleic acids. The absence of HGPRT is not a problem for these cells unless the de novo purine synthesis pathway is also disrupted. Exposing cells to aminopterin (a folic acid analogue which inhibits dihydrofolate reductase) makes them unable to use the de novo pathway and become fully auxotrophic for nucleic acids, thus requiring supplementation to survive.

The selective culture medium is called HAT medium because it contains hypoxanthine, aminopterin and thymidine. This medium is selective for fused (hybridoma) cells. Unfused myeloma cells cannot grow because they lack HGPRT and thus cannot replicate their DNA. Unfused spleen cells cannot grow indefinitely because of their limited life span. Only fused hybrid cells referred to as hybridomas, are able to grow indefinitely in the medium because the spleen cell partner supplies HGPRT and the myeloma partner has traits that make it immortal (similar to a cancer cell).

This mixture of cells is then diluted and clones are grown from single parent cells on microtitre wells. The antibodies secreted by the different clones are then assayed for their ability to bind to the antigen (with a test such as ELISA or antigen microarray assay) or immuno-dot blot. The most productive and stable clone is then selected for future use.

The hybridomas can be grown indefinitely in a suitable cell culture medium. They can also be injected into mice (in the peritoneal cavity, surrounding the gut). There, they produce tumors secreting an antibody-rich fluid called ascites fluid.

The medium must be enriched during in vitro selection to further favour hybridoma growth. This can be achieved by the use of a layer of feeder fibrocyte cells or supplement medium such as briclone. Culture-media conditioned by macrophages can be used. Production in cell culture is usually preferred as the ascites technique is painful to the animal. Where alternate techniques exist, ascites is considered unethical. [15]

Novel mAb development technology

Several monoclonal antibody technologies have been developed recently, [16] such as phage display, [17] single B cell culture, [18] single cell amplification from various B cell populations [19] [20] [21] [22] [23] and single plasma cell interrogation technologies. Different from traditional hybridoma technology, the newer technologies use molecular biology techniques to amplify the heavy and light chains of the antibody genes by PCR and produce in either bacterial or mammalian systems with recombinant technology. One of the advantages of the new technologies is applicable to multiple animals, such as rabbit, llama, chicken and other common experimental animals in the laboratory.

Purification

After obtaining either a media sample of cultured hybridomas or a sample of ascites fluid, the desired antibodies must be extracted. Cell culture sample contaminants consist primarily of media components such as growth factors, hormones and transferrins. In contrast, the in vivo sample is likely to have host antibodies, proteases, nucleases, nucleic acids and viruses. In both cases, other secretions by the hybridomas such as cytokines may be present. There may also be bacterial contamination and, as a result, endotoxins that are secreted by the bacteria. Depending on the complexity of the media required in cell culture and thus the contaminants, one or the other method (in vivo or in vitro) may be preferable.

The sample is first conditioned, or prepared for purification. Cells, cell debris, lipids, and clotted material are first removed, typically by centrifugation followed by filtration with a 0.45 μm filter. These large particles can cause a phenomenon called membrane fouling in later purification steps. In addition, the concentration of product in the sample may not be sufficient, especially in cases where the desired antibody is produced by a low-secreting cell line. The sample is therefore concentrated by ultrafiltration or dialysis.

Most of the charged impurities are usually anions such as nucleic acids and endotoxins. These can be separated by ion exchange chromatography. [24] Either cation exchange chromatography is used at a low enough pH that the desired antibody binds to the column while anions flow through, or anion exchange chromatography is used at a high enough pH that the desired antibody flows through the column while anions bind to it. Various proteins can also be separated along with the anions based on their isoelectric point (pI). In proteins, the isoelectric point (pI) is defined as the pH at which a protein has no net charge. When the pH > pI, a protein has a net negative charge, and when the pH < pI, a protein has a net positive charge. For example, albumin has a pI of 4.8, which is significantly lower than that of most monoclonal antibodies, which have a pI of 6.1. Thus, at a pH between 4.8 and 6.1, the average charge of albumin molecules is likely to be more negative, while mAbs molecules are positively charged and hence it is possible to separate them. Transferrin, on the other hand, has a pI of 5.9, so it cannot be easily separated by this method. A difference in pI of at least 1 is necessary for a good separation.

Transferrin can instead be removed by size exclusion chromatography. This method is one of the more reliable chromatography techniques. Since we are dealing with proteins, properties such as charge and affinity are not consistent and vary with pH as molecules are protonated and deprotonated, while size stays relatively constant. Nonetheless, it has drawbacks such as low resolution, low capacity and low elution times.

A much quicker, single-step method of separation is protein A/G affinity chromatography. The antibody selectively binds to protein A/G, so a high level of purity (generally >80%) is obtained. The generally harsh conditions of this method may damage easily damaged antibodies. A low pH can break the bonds to remove the antibody from the column. In addition to possibly affecting the product, low pH can cause protein A/G itself to leak off the column and appear in the eluted sample. Gentle elution buffer systems that employ high salt concentrations are available to avoid exposing sensitive antibodies to low pH. Cost is also an important consideration with this method because immobilized protein A/G is a more expensive resin.

To achieve maximum purity in a single step, affinity purification can be performed, using the antigen to provide specificity for the antibody. In this method, the antigen used to generate the antibody is covalently attached to an agarose support. If the antigen is a peptide, it is commonly synthesized with a terminal cysteine, which allows selective attachment to a carrier protein, such as KLH during development and to support purification. The antibody-containing medium is then incubated with the immobilized antigen, either in batch or as the antibody is passed through a column, where it selectively binds and can be retained while impurities are washed away. An elution with a low pH buffer or a more gentle, high salt elution buffer is then used to recover purified antibody from the support.

Antibody heterogeneity

Product heterogeneity is common in monoclonal antibodies and other recombinant biological products and is typically introduced either upstream during expression or downstream during manufacturing. [25] [26] [27]

These variants are typically aggregates, deamidation products, glycosylation variants, oxidized amino acid side chains, as well as amino and carboxyl terminal amino acid additions. [28] These seemingly minute structural changes can affect preclinical stability and process optimization as well as therapeutic product potency, bioavailability and immunogenicity. The generally accepted purification method of process streams for monoclonal antibodies includes capture of the product target with protein A, elution, acidification to inactivate potential mammalian viruses, followed by ion chromatography, first with anion beads and then with cation beads.[ citation needed ]

Displacement chromatography has been used to identify and characterize these often unseen variants in quantities that are suitable for subsequent preclinical evaluation regimens such as animal pharmacokinetic studies. [29] [30] Knowledge gained during the preclinical development phase is critical for enhanced product quality understanding and provides a basis for risk management and increased regulatory flexibility. The recent Food and Drug Administration's Quality by Design initiative attempts to provide guidance on development and to facilitate design of products and processes that maximizes efficacy and safety profile while enhancing product manufacturability. [31]

Recombinant

The production of recombinant monoclonal antibodies involves repertoire cloning, CRISPR/Cas9, or phage display/yeast display technologies. [32] Recombinant antibody engineering involves antibody production by the use of viruses or yeast, rather than mice. These techniques rely on rapid cloning of immunoglobulin gene segments to create libraries of antibodies with slightly different amino acid sequences from which antibodies with desired specificities can be selected. [33] The phage antibody libraries are a variant of phage antigen libraries. [34] These techniques can be used to enhance the specificity with which antibodies recognize antigens, their stability in various environmental conditions, their therapeutic efficacy and their detectability in diagnostic applications. [35] Fermentation chambers have been used for large scale antibody production.

Chimeric antibodies

While mouse and human antibodies are structurally similar, the differences between them were sufficient to invoke an immune response when murine monoclonal antibodies were injected into humans, resulting in their rapid removal from the blood, as well as systemic inflammatory effects and the production of human anti-mouse antibodies (HAMA).

Recombinant DNA has been explored since the late 1980s to increase residence times. In one approach called "CDR grafting", [36] mouse DNA encoding the binding portion of a monoclonal antibody was merged with human antibody-producing DNA in living cells. The expression of this "chimeric" or "humanised" DNA through cell culture yielded part-mouse, part-human antibodies. [37] [38]

Human antibodies

Approaches have been developed to isolate human monoclonal antibodies. Isolation of human monoclonal antibodies. .tif
Approaches have been developed to isolate human monoclonal antibodies.

Ever since the discovery that monoclonal antibodies could be generated, scientists have targeted the creation of fully human products to reduce the side effects of humanised or chimeric antibodies. Several successful approaches have been proposed: transgenic mice, [39] phage display [17] and single B cell cloning. [16]

Cost

Monoclonal antibodies are more expensive to manufacture than small molecules due to the complex processes involved and the general size of the molecules, all in addition to the enormous research and development costs involved in bringing a new chemical entity to patients. They are priced to enable manufacturers to recoup the typically large investment costs, and where there are no price controls, such as the United States, prices can be higher if they provide great value. Seven University of Pittsburgh researchers concluded, "The annual price of mAb therapies is about $100,000 higher in oncology and hematology than in other disease states", comparing them on a per patient basis, to those for cardiovascular or metabolic disorders, immunology, infectious diseases, allergy, and ophthalmology. [40]

Applications

Diagnostic tests

Once monoclonal antibodies for a given substance have been produced, they can be used to detect the presence of this substance. Proteins can be detected using the Western blot and immuno dot blot tests. In immunohistochemistry, monoclonal antibodies can be used to detect antigens in fixed tissue sections, and similarly, immunofluorescence can be used to detect a substance in either frozen tissue section or live cells.

Analytic and chemical uses

Antibodies can also be used to purify their target compounds from mixtures, using the method of immunoprecipitation.

Therapeutic uses

Therapeutic monoclonal antibodies act through multiple mechanisms, such as blocking of targeted molecule functions, inducing apoptosis in cells which express the target, or by modulating signalling pathways. [41] [42] [43]

Cancer treatment

One possible treatment for cancer involves monoclonal antibodies that bind only to cancer-cell-specific antigens and induce an immune response against the target cancer cell. Such mAbs can be modified for delivery of a toxin, radioisotope, cytokine or other active conjugate or to design bispecific antibodies that can bind with their Fab regions both to target antigen and to a conjugate or effector cell. Every intact antibody can bind to cell receptors or other proteins with its Fc region.

Monoclonal antibodies for cancer. ADEPT, antibody directed enzyme prodrug therapy; ADCC: antibody dependent cell-mediated cytotoxicity; CDC: complement-dependent cytotoxicity; MAb: monoclonal antibody; scFv, single-chain Fv fragment. Monoclonal antibodies.svg
Monoclonal antibodies for cancer. ADEPT, antibody directed enzyme prodrug therapy; ADCC: antibody dependent cell-mediated cytotoxicity; CDC: complement-dependent cytotoxicity; MAb: monoclonal antibody; scFv, single-chain Fv fragment.

MAbs approved by the FDA for cancer include: [45]

Autoimmune diseases

Monoclonal antibodies used for autoimmune diseases include infliximab and adalimumab, which are effective in rheumatoid arthritis, Crohn's disease, ulcerative colitis and ankylosing spondylitis by their ability to bind to and inhibit TNF-α. [46] Basiliximab and daclizumab inhibit IL-2 on activated T cells and thereby help prevent acute rejection of kidney transplants. [46] Omalizumab inhibits human immunoglobulin E (IgE) and is useful in treating moderate-to-severe allergic asthma.

Examples of therapeutic monoclonal antibodies

Monoclonal antibodies for research applications can be found directly from antibody suppliers, or through use of a specialist search engine like CiteAb. Below are examples of clinically important monoclonal antibodies.

Main categoryTypeApplicationMechanism/TargetMode
Anti-
inflammatory		 infliximab [46] inhibits TNF-α chimeric
adalimumab inhibits TNF-α human
ustekinumab blocks interleukin IL-12 and IL-23 human
basiliximab [46] inhibits IL-2 on activated T cells chimeric
daclizumab [46] inhibits IL-2 on activated T cells humanized
omalizumab inhibits human immunoglobulin E (IgE)humanized
Anti-cancer gemtuzumab [46] targets myeloid cell surface antigen CD33 on leukemia cellshumanized
alemtuzumab [46] targets an antigen CD52 on T- and B-lymphocytes humanized
rituximab [46] targets phosphoprotein CD20 on B lymphocytes chimeric
trastuzumab
  • breast cancer with HER2/neu overexpression
targets the HER2/neu (erbB2) receptorhumanized
nimotuzumab EGFR inhibitorhumanized
cetuximab EGFR inhibitorchimeric
panitumumab EGFR inhibitorhuman
bevacizumab & ranibizumab inhibits VEGF humanized
Anti-cancer and anti-viral bavituximab [47] immunotherapy, targets phosphatidylserine [47] chimeric
Anti-viral

casirivimab/imdevimab [48]

immunotherapy, targets spike protein of SARS-CoV-2 human
bamlanivimab/etesevimab [49] immunotherapy, targets spike protein of SARS-CoV-2 human
Sotrovimab [50] immunotherapy, targets spike protein of SARS-CoV-2 human
Other palivizumab [46]
  • RSV infections in children
inhibits an RSV fusion (F) proteinhumanized
abciximab [46] inhibits the receptor GpIIb/IIIa on platelets chimeric

COVID-19

In 2020, the monoclonal antibody therapies bamlanivimab/etesevimab and casirivimab/imdevimab were given emergency use authorizations by the US Food and Drug Administration to reduce the number of hospitalizations, emergency room visits, and deaths because of COVID-19. [48] [49] In September 2021, the Biden administration purchased US$2.9 billion worth of Regeneron monoclonal antibodies at $2,100 per dose to curb the shortage. [51]

As of December 2021, in vitro neutralization tests indicate monoclonal antibody therapies (with the exception of sotrovimab and tixagevimab/cilgavimab) were not likely to be active against the Omicron variant. [52]

Over 2021–22, two Cochrane reviews found insufficient evidence for using neutralizing monoclonal antibodies to treat COVID-19 infections. [53] [54] The reviews applied only to people who were unvaccinated against COVID‐19, and only to the COVID-19 variants existing during the studies, not to newer variants, such as Omicron. [54]

In March 2024, pemivibart, a monoclonal antibody drug, received an emergency use authorization from the US FDA for use as pre-exposure prophylaxis to protect certain moderately to severely immunocompromised individuals against COVID-19. [55] [56]

Side effects

Several monoclonal antibodies, such as bevacizumab and cetuximab, can cause different kinds of side effects. [57] These side effects can be categorized into common and serious side effects. [58]

Some common side effects include:

Among the possible serious side effects are: [59]

See also

Related Research Articles

<span class="mw-page-title-main">Hybridoma technology</span> Method for producing lots of identical antibodies

Hybridoma technology is a method for producing large numbers of identical antibodies, also called monoclonal antibodies. This process starts by injecting a mouse with an antigen that provokes an immune response. A type of white blood cell, the B cell, produces antibodies that bind to the injected antigen. These antibody producing B-cells are then harvested from the mouse and, in turn, fused with immortal myeloma cancer cells, to produce a hybrid cell line called a hybridoma, which has both the antibody-producing ability of the B-cell and the longevity and reproductivity of the myeloma.

<span class="mw-page-title-main">Phage display</span> Biological technique to evolve proteins using bacteriophages

Phage display is a laboratory technique for the study of protein–protein, protein–peptide, and protein–DNA interactions that uses bacteriophages to connect proteins with the genetic information that encodes them. In this technique, a gene encoding a protein of interest is inserted into a phage coat protein gene, causing the phage to "display" the protein on its outside while containing the gene for the protein on its inside, resulting in a connection between genotype and phenotype. The proteins that the phages are displaying can then be screened against other proteins, peptides or DNA sequences, in order to detect interaction between the displayed protein and those of other molecules. In this way, large libraries of proteins can be screened and amplified in a process called in vitro selection, which is analogous to natural selection.

<span class="mw-page-title-main">Single-chain variable fragment</span> Fragment

A single-chain variable fragment (scFv) is not actually a fragment of an antibody, but instead is a fusion protein of the variable regions of the heavy (VH) and light chains (VL) of immunoglobulins, connected with a short linker peptide of ten to about 25 amino acids. The linker is usually rich in glycine for flexibility, as well as serine or threonine for solubility, and can either connect the N-terminus of the VH with the C-terminus of the VL, or vice versa. This protein retains the specificity of the original immunoglobulin, despite removal of the constant regions and the introduction of the linker. The image to the right shows how this modification usually leaves the specificity unaltered.

<span class="mw-page-title-main">Cancer immunotherapy</span> Artificial stimulation of the immune system to treat cancer

Cancer immunotherapy (immuno-oncotherapy) is the stimulation of the immune system to treat cancer, improving the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology (immuno-oncology) and a growing subspecialty of oncology.

<span class="mw-page-title-main">Single-domain antibody</span> Antibody fragment

A single-domain antibody (sdAb), also known as a Nanobody, is an antibody fragment consisting of a single monomeric variable antibody domain. Like a whole antibody, it is able to bind selectively to a specific antigen. With a molecular weight of only 12–15 kDa, single-domain antibodies are much smaller than common antibodies which are composed of two heavy protein chains and two light chains, and even smaller than Fab fragments and single-chain variable fragments.

A biopharmaceutical, also known as a biological medical product, or biologic, is any pharmaceutical drug product manufactured in, extracted from, or semisynthesized from biological sources. Different from totally synthesized pharmaceuticals, they include vaccines, whole blood, blood components, allergenics, somatic cells, gene therapies, tissues, recombinant therapeutic protein, and living medicines used in cell therapy. Biologics can be composed of sugars, proteins, nucleic acids, or complex combinations of these substances, or may be living cells or tissues. They are isolated from living sources—human, animal, plant, fungal, or microbial. They can be used in both human and animal medicine.

Humanized antibodies are antibodies from non-human species whose protein sequences have been modified to increase their similarity to antibody variants produced naturally in humans. The process of "humanization" is usually applied to monoclonal antibodies developed for administration to humans. Humanization can be necessary when the process of developing a specific antibody involves generation in a non-human immune system. The protein sequences of antibodies produced in this way are partially distinct from homologous antibodies occurring naturally in humans, and are therefore potentially immunogenic when administered to human patients. The International Nonproprietary Names of humanized antibodies end in -zumab, as in omalizumab.

Muromonab-CD3 is an immunosuppressant medication given to reduce acute rejection in people with organ transplants. It is a monoclonal antibody targeted at the CD3 receptor, a membrane protein on the surface of T cells. It is the first monoclonal antibody to be approved for clinical use in humans.

<span class="mw-page-title-main">Protein A</span> Surface protein in bacteria cell walls

Protein A is a 42 kDa surface protein originally found in the cell wall of the bacteria Staphylococcus aureus. It is encoded by the spa gene and its regulation is controlled by DNA topology, cellular osmolarity, and a two-component system called ArlS-ArlR. It has found use in biochemical research because of its ability to bind immunoglobulins. It is composed of five homologous Ig-binding domains that fold into a three-helix bundle. Each domain is able to bind proteins from many mammalian species, most notably IgGs. It binds the heavy chain within the Fc region of most immunoglobulins and also within the Fab region in the case of the human VH3 family. Through these interactions in serum, where IgG molecules are bound in the wrong orientation, the bacteria disrupts opsonization and phagocytosis.

<span class="mw-page-title-main">Monoclonal antibody therapy</span> Form of immunotherapy

Monoclonal antibodies (mAbs) have varied therapeutic uses. It is possible to create a mAb that binds specifically to almost any extracellular target, such as cell surface proteins and cytokines. They can be used to render their target ineffective, to induce a specific cell signal, to cause the immune system to attack specific cells, or to bring a drug to a specific cell type.

A bispecific monoclonal antibody is an artificial protein that can simultaneously bind to two different types of antigen or two different epitopes on the same antigen. Naturally occurring antibodies typically only target one antigen. BsAbs can be manufactured in several structural formats. BsAbs can be designed to recruit and activate immune cells, to interfere with receptor signaling and inactivate signaling ligands, and to force association of protein complexes. BsAbs have been explored for cancer immunotherapy, drug delivery, and Alzheimer's disease.

<span class="mw-page-title-main">Bi-specific T-cell engager</span> Class of artificial monoclonal antibodies

Bi-specific T-cell engager (BiTE) is a class of artificial bispecific monoclonal antibodies that are investigated for use as anti-cancer drugs. They direct a host's immune system, more specifically the T cells' cytotoxic activity, against cancer cells. BiTE is a registered trademark of Micromet AG.

Siltuximab (INN), sold under the brand name Sylvant, is used for the treatment of people with multicentric Castleman's disease. It is a chimeric monoclonal antibody that binds to interleukin-6. It is an interleukin-6 (IL-6) antagonist.

A neutralizing antibody (NAb) is an antibody that defends a cell from a pathogen or infectious particle by neutralizing any effect it has biologically. Neutralization renders the particle no longer infectious or pathogenic. Neutralizing antibodies are part of the humoral response of the adaptive immune system against viruses, bacteria and microbial toxin. By binding specifically to surface structures (antigen) on an infectious particle, neutralizing antibodies prevent the particle from interacting with its host cells it might infect and destroy.

<span class="mw-page-title-main">Trifunctional antibody</span> Monoclonal antibody

A trifunctional antibody is a monoclonal antibody with binding sites for two different antigens, typically CD3 and a tumor antigen, making it a type of bispecific monoclonal antibody. In addition, its intact Fc-part can bind to an Fc receptor on accessory cells like conventional monospecific antibodies. The net effect is that this type of drug links T cells and monocytes/macrophages, natural killer cells, dendritic cells or other Fc receptor expressing cells to the tumor cells, leading to their destruction.

A rabbit hybridoma is a hybrid cell line formed by the fusion of an antibody producing rabbit B cell with a cancerous B-cell (myeloma).

<span class="mw-page-title-main">ImmTAC</span> Biological drug for the treatment of cancer

ImmTACs are a class of bispecific biological drug being investigated for the treatment of cancer and viral infections which combines engineered cancer-recognizing TCRs with immune activating complexes. ImmTACs target cancerous or virally infected cells through binding human leukocyte antigen (HLA) presented peptide antigens and redirect the host's cytotoxic T cells to recognise and kill them.

MDX-1097 is a monoclonal antibody therapy that in 2023 has been assessed in a Phase IIb clinical trial in conjunction with lenalidomide and dexamethasone as a treatment for multiple myeloma, a type of white blood cell cancer. MDX-1097 was originally developed by scientists at Immune System Therapeutics Ltd. In 2015, Haemalogix Ltd acquired the rights to MDX-1097 and are taking it through clinical testing.

Recombinant antibodies are antibody fragments produced by using recombinant antibody coding genes. They mostly consist of a heavy and light chain of the variable region of immunoglobulin. Recombinant antibodies have many advantages in both medical and research applications, which make them a popular subject of exploration and new production against specific targets. The most commonly used form is the single chain variable fragment (scFv), which has shown the most promising traits exploitable in human medicine and research. In contrast to monoclonal antibodies produced by hybridoma technology, which may lose the capacity to produce the desired antibody over time or the antibody may undergo unwanted changes, which affect its functionality, recombinant antibodies produced in phage display maintain high standard of specificity and low immunogenicity.

Passive antibody therapy, also called serum therapy, is a subtype of passive immunotherapy that administers antibodies to target and kill pathogens or cancer cells. It is designed to draw support from foreign antibodies that are donated from a person, extracted from animals, or made in the laboratory to elicit an immune response instead of relying on the innate immune system to fight disease. It has a long history from the 18th century for treating infectious diseases and is now a common cancer treatment. The mechanism of actions include: antagonistic and agonistic reaction, complement-dependent cytotoxicity (CDC), and antibody-dependent cellular cytotoxicity (ADCC).

References

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