by Introduction to Monoclonal Antibody Therapeutics
Unlike polyclonal antibodies that occur naturally in the body and recognize multiple targets, monoclonal antibodies are exact replicas aimed at one and only one target such as a virus, bacteria or tumor cell. They were first discovered in 1975 by Cesar Milstein and Georges Kohler for which they received the Nobel Prize in Medicine in 1984. Since then, monoclonal antibody technology has revolutionized the therapeutic landscape and become a mainstay in modern medicine.
Mechanism of Action
Monoclonal antibodies typically act by binding to target receptors or proteins and interfere with their function. Some key mechanisms of action include blocking receptor activation, recruitment of immune cells to target foreign or tumor cells, interfering with receptor signaling cascades, neutralizing toxins or microbial virulence factors, complement dependent cytotoxicity of target cells amongst others. This specific binding allows monoclonal antibodies to act with high precision and cause minimal off-target effects.
Therapeutic Applications
Oncology has been one of the major application areas of Monoclonal Antibody Therapeutics. As early as 1997, rituximab became the first monoclonal antibody approved for treatment of non-Hodgkin’s lymphoma. Since then numerous antibody drugs targeting different tumor receptors and antigens have been developed. Some examples include trastuzumab for breast cancer, cetuximab for colorectal cancer, alemtuzumab for chronic lymphocytic leukemia and bevacizumab for various solid tumors. The recent approvals of pembrolizumab and nivolumab for various types of cancer have ushered in a new era of cancer immunotherapy using checkpoint inhibitors.
In infectious diseases, monoclonal antibodies targeting pathogens have shown promise both for prophylaxis and treatment of infections. Palivizumab is approved for prevention of respiratory syncytial virus in high-risk infants. Bezlotoxumab targets Clostridium difficile infection while therapies for Ebola and Middle East respiratory syndrome are under development. In autoimmune disorders, rituximab has transformed the treatment landscape for rheumatoid arthritis while eculizumab targets paroxysmal nocturnal hemoglobinuria. For maintenance of remission in inflammatory bowel disease, vedolizumab and natalizumab have emerged as important treatment options.
Monoclonal antibodies have also made their way into cardiovascular and metabolic diseases. Alirocumab and evolocumab target PCSK9 to lower LDL cholesterol levels while canakinumab targets IL-1β to reduce risk of recurrent cardiovascular events in patients with a history of myocardial infarction. In neurology, adalimumab and daclizumab are approved for treatment of multiple sclerosis while emerging therapies target Alzheimer’s and Parkinson’s disease. In hematology, blinatumomab is a promising bispecific T-cell engager for treatment of acute lymphoblastic leukemia and non-Hodgkin’s lymphoma.
Challenges and Future Directions
While monoclonal antibody therapeutics have delivered astounding clinical benefits, there are also key challenges that need to be addressed. High production costs, requirement of specialized cold chain storage and transportation and intravenous mode of administration are some practical limitations. Immunogenicity especially with repeated or long-term dosing continues to remain an issue. Selection of right biomarkers for patient stratification and understanding predictive factors of response and resistance can further enhance clinical efficacy. Key areas of ongoing research include development of bispecific antibodies, antibody drug conjugates, long-acting antibodies, multi-valent antibodies and combination therapies.
advances in antibody engineering are enabling development of next-generation formats such as single chain variable fragments, antibody fragments, nanobodies and CAR-T cell therapies. As newer recombinant technologies further drive down costs and overcome current challenges, monoclonal antibodies hold tremendous promise to transform healthcare by enabling personalized, precise medicine for a diverse range of diseases.
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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
