CAR-T Cell Therapy: Advancements and Future Perspectives
The Chimeric antigen receptor CAR-T cell therapy has revolutionized the immunotherapy field with its high success rate against hematological diseases. Investigations in the early 1980s conceived the idea about tumor-infiltrating lymphocytes; however, reproducibility in invitro hampered further developments. It was not until 1993 Immunologist Dr. Zelig Eshhar created the first generation of chimeric T cells at the Weizmann Institute, Israel. The first-generation was successful during experiments, although not clinically effective. Since then, over three decades, a significant chunk of scientific intellect and considerable Research in cancer immunology has optimized this technology further.
Stepping forward to 2021, we got 5 FDA-approved drugs, Diverse manufacturing platforms, an estimated billion-dollar market, and more than 250 players have invested their portfolios into generating/marketing/manufacturing CAR-T-based therapeutics. Furthermore, now CAR T-based therapies have expanded their horizon into diseases other than oncology, ranging from viral infections such as HIV, CMV to Autoimmune disorders. Ongoing COVID-19 too finds itself in soup as NCT04324996 sponsored by Chongqing Public Health Medical Centre is currently in phase 2.
However, after decades of modifications, Research & trials, the question remains about its efficacy against solid tumors, recent advancements, who are the key players developing platforms for next-generation CARs? And the next big breakthrough in this field.
The CARs Generation:
CARs are divided predominantly into three generations; however, incorporating multiple intracellular domains has made them more advanced as the next generation. The division is according to their intracellular signaling domains.
The first generation: comprise one extracellular domain (scFv) and an intracellular CD3ζ domain.
Second-generation: CARs have a unique costimulatory part derived from CD28 that significantly improved their clinical efficacy during treatment by increasing the survival of modified T lymphocytes.
The third generation: consists of molecules having three or more cytosolic costimulatory domains. In addition to CD28, 4-1BB, CD27, ICOS, OX40 can be coupled that significantly increase the activation, survival, and potency of the genetically engineered T lymphocytes. However, the second-generation CARs have shown the best clinical outcomes and safety to date.
Next-generation: Consists of One or more intracellular domains.
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