Title:Chimeric Antigen Receptor T-cell Therapy in Cancer: A Critical Review
Volume: 15
Issue: 3
Author(s): Ravikant Sharma, Lalitha Suravarjhula, Madhuparna Banerjee, Gautam Kumar and Nitesh Kumar*
Affiliation:
- Department of Pharmacology and Toxicology, National Institution of Pharmaceutical Education
and Research, Hajipur, Vaishali, Bihar, 844102, India
Keywords:
CAR-T Cell, CD3, CD28, CD19, bispecific T-cell products, cancer.
Abstract: Targeted cancer therapy acts on targeted molecules, is less toxic to normal cells, and
acts more specifically on cancer cells. The two primary strategies for preventing malignancy
growth are the blocking of T-cell repression signals or forwarding of T-cell to tumor target with
both T and tumor-specific antibodies. The CAR comprises three domains, the extracellular antigen
recognition domain and the intracellular T-cell signaling domain, which participate in activating
T-cells. The two most common adverse effects of CAR T-cell treatment are cytokine release syndrome
(CRS) and cell-associated neurotoxicity syndrome (CANS). The adaptability of intracellular
signaling domains inside CARs allows the cell to counterbalance the downregulation of costimulatory
molecules produced by tumor cells, either indirectly or directly. The major disadvantage
of CAR-T cell therapy is off-target toxicity. Treatment with CARs expressing CD3,
CD123, Lewis Y, CLL-1, CD44v6, FLT3, and folate receptors showed promising results in preclinical
models of acute myeloid leukemia (AML). A recent study has revealed that B7-H3 CART
cells exhibit significant anticancer efficacy in a variety of solid tumor preclinical models, including
PDAC, ovarian cancer, neuroblastoma, and various pediatric malignancies. The notion of
SUPRA CAR, with its unique capacity to alter targets without the need to re-engineer, is a recent
innovation in CAR. Given the importance of NK cells in tumor development and metastatic defence,
NK cell-based immunotherapies, including adoptive transfer of NK cells, have garnered a
lot of interest. With the advancement of improved cellular manufacturing methods, novel cellular
engineering strategies, precision genome editing technologies, and combination therapy approaches,
we firmly believe that CAR-T cells will soon become an off-the-shelf, cost-effective, and potentially
curative therapy for oncogenesis.
