CAR-T Cell Therapy: Advancements and Future Perspectives

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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 CD3? 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.
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Next-generation Consists of One or more
intracellular domains. For the complete in-depth
article on CAR-T Cell Therapy, please visit
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