Biotechnology has enabled the production of therapeutic antibodies and proteins that can treat a wide range of diseases. Through recombinant DNA technology, scientists are now able to manufacture antibodies and proteins outside living organisms for therapeutic purposes. This has paved way for the development of groundbreaking recombinant therapeutic antibodies and proteins that are transforming the treatment of chronic illnesses.
Development of Recombinant Therapeutic Antibodies
Producing antibodies recombinantly involves isolation of antibody-encoding genes and transfer of these genes into host cells for expression. Once genes encoding the antibody parts are isolated, they are inserted into engineered host cells which are then cultured to allow high-level production of the recombinant antibody. The first therapeutic antibody approved by the FDA was a mouse-human chimeric antibody called Orthoclone OKT3 in 1986 for prevention of kidney transplant rejection. Since then, development of humanized and fully human antibodies has significantly reduced immunogenicity issues. Today, majority of therapeutic antibodies approved are human or humanized. Some key developments include production of the first monoclonal antibody drug infliximab in 1998 and development of bispecific T-cell engaging antibodies to enhance targeting of cancer cells. Continuous engineering of host cells also allows higher yields and more efficient production processes.
Applications in Cancer Treatment
Recombinant antibodies have brought about major advances in cancer therapy. Monoclonal antibodies that target tumor antigens help in improving survival rates. Trastuzumab for HER2-positive breast cancer was a breakthrough. Other established antibodies include rituximab for lymphoma, bevacizumab for several cancers and cetuximab for colorectal cancer. Antibody-drug conjugates enable targeted delivery of cytotoxic payloads to tumor cells. Adcetris for Hodgkin’s lymphoma was the first such conjugate approved. Bispecific T-cell engagers are the latest class showing promise in directing T cells to kill cancer cells. Despite improvements, resistance does occur requiring development of next-generation antibodies. Promising areas include immune checkpoint inhibitors and engineered antibodies with multiple binding domains.
Role in Management of Autoimmune Disorders
Therapeutic antibodies also dominate treatment of numerous autoimmune disorders. Infliximab and adalimumab for rheumatoid arthritis helped transform its management. Etanercept was the first approved biologic for this condition. For multiple sclerosis, natalizumab aids in reducing relapse rates. Severe asthma can be controlled using omalizumab by blocking immunoglobulin E. In inflammatory bowel disease, infliximab and adalimumab induce remission in Crohn’s disease and ulcerative colitis patients. Novel targets continue being explored with antibodies against molecules like IL-17 showing benefit in psoriasis patients. By neutralizing specific targets, these antibodies dampen the overactive immune response without generalized immunosuppression. This has greatly improved outcomes with generally safe side effect profiles.
Biosimilars – Expanding Accessibility
Patent expiries of top selling antibodies will boost availability of biosimilar versions at lower costs. While biosimilars aim to be highly similar, establishing equivalence requires rigorous comparability studies. The European Medicines Agency and FDA have laid down guidelines. Approval of the first biosimilar infliximab in 2013 opened floodgates worldwide. AbbVie’s Humira already faces competition following patent expiry. Market entry of proposed adalimumab biosimilars is also awaited. Greater accessibility through biosimilars will be crucial for developing nations to expand use of these life-saving therapies. However, determining interchangeability remains challenging given complexity of large molecules. Post marketing pharmacovigilance must also be strengthened to monitor long term safety and immunogenicity of switching between reference and biosimilar products.
Recombinant therapeutic antibodies and proteins have emerged as major biopharmaceutical successes in managing previously inadequately treated chronic diseases. Further engineering using advanced technologies holds promise to develop more potent and safer next-generation molecules. Their applications continue widening with exploration of new targets. Biosimilars will enhance global access, supported by pharmacovigilance. Targeted proteomics may aid development of personalized medicine approaches through patient selection and monitoring of responses. Overall, this class has revolutionized treatment paradigms and improved quality of many lives worldwide.
1. Source: Coherent Market Insights, Public sources, Desk research
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