by Introduction to Monoclonal Antibody Therapeutics
Monoclonal antibodies (mAbs) are lab-made proteins that act like human antibodies in the immune system. They target and bind to specific proteins, called antigens, on cells and in blood. Each monoclonal antibody is designed to recognize and bind to only one specific type of antigen. Because of this selective targeting ability, mAbs can be used to treat diseases by blocking the specific molecules that cause disease or tag them for destruction by the immune system.
History and Development of Monoclonal Antibody Therapeutics
The idea of using antibodies in treatment was first proposed in the 1970s and the first monoclonal antibodies were developed in 1975 by scientists César Milstein and Georges Köhler. They genetically engineered mouse-derived myeloma cells to produce a specific antibody. Monoclonal Antibody Therapeutics This breakthrough technique allowed production of unlimited quantities of antibodies that specifically target a single antigen. In the 1980s, advances led to development of the first mAbs to treat cancer and other conditions. The US Food and Drug Administration approved the first therapeutic mAb, Rituximab, in 1997 for treatment of lymphoma. Since then, over 60 mAb drugs have been approved to treat various cancers, autoimmune diseases, eye disorders and other conditions.
Mechanisms of Action
Monoclonal antibodies work through various mechanisms:
– Blocking: They can bind directly to extracellular targets such as cell surface receptors or immune system mediators to block their biologic function and prevent downstream signaling. This suppresses disease-causing pathways.
– Depletion: Certain mAbs recruit immune cells to directly kill antibody-tagged cells by a process called antibody-dependent cellular cytotoxicity. This is how anti-cancer antibodies like Rituximab eliminate tumor cells.
– Complement activation: Some trigger the complement system, a complex series of plasma proteins that lead to inflammatory response and targeted cell destruction.
– Interfering with binding: They can interfere with molecular interactions by binding to ligands or receptors and preventing their binding and downstream activation of signaling.
Applications in Cancer Treatment
Many monoclonal antibody drugs have revolutionized cancer therapy. They provide more targeted treatment options compared to conventional chemotherapy. Some examples include:
– Rituximab is used for lymphoma, targeting the CD20 antigen on B-cells.
– Trastuzumab treats HER2-positive breast cancers by blocking the HER2 receptor signaling pathway.
– Cetuximab and Panitumumab treat colorectal cancers by blocking the epidermal growth factor receptor (EGFR) pathway.
– Nivolumab and Pembrolizumab are immune checkpoint inhibitors used in many cancers. They block PD-1 and PD-L1 proteins to unleash anti-tumor immune responses.
– Blinatumomab treats some leukemias by binding CD19 on leukemia cells and CD3 on T cells to recruit the immune system against cancer.
Applications Beyond Cancer
Monoclonal antibodies have wide applications in other diseases:
– Adalimumab, infliximab and others treat autoimmune diseases like rheumatoid arthritis by neutralizing tumor necrosis factor (TNF), a cytokine that drives inflammation.
– Ranibizumab was the first mAb approved for age-related macular degeneration, treating the wet form by inhibiting vascular endothelial growth factor A (VEGF-A).
– Palivizumab prevents respiratory syncytial virus infections in high-risk infants by binding the virus’s F glycoprotein.
– Omalizumab treats allergic asthma by binding to immunoglobulin E (IgE) and preventing its effects.
Advancements and Future Potential
Newer modifications allow mAbs to have enhanced potency, safety and pharmacological properties. Antibody-drug conjugates link cytotoxic drugs to antibodies to selectively deliver chemotherapeutics to tumor cells. Bispecific antibodies can bind two different antigens simultaneously and improve targeting of tumor cells.
chimeric antigen receptor (CAR) T-cell therapy engineers patient’s T cells to produce chimeric antigen receptors that guide immune attacks on cancer cells. With evolving technology, monoclonal antibodies hold immense promise for transforming treatment across a wide spectrum of diseases in the future.
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1.Source: Coherent Market Insights, Public sources, Desk research
2.We have leveraged AI tools to mine information and compile it
