Potential of Chimeric Antigen Receptor T-Cells in Cancer Therapy
Novel approaches for targeted delivery like nanoparticles, liposomes, polymer conjugates, etc. with better safety profile needs to be developed for cancer treatment. Chimeric antigen receptors (CAR) with modified thymus cells (T-cells) showed greater pote
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Potential of Chimeric Antigen Receptor T-Cells in Cancer Therapy Drashti Desai, R. S. Gaud, and Pravin Shende
Abstract
Novel approaches for targeted delivery like nanoparticles, liposomes, polymer conjugates, etc. with better safety profile needs to be developed for cancer treatment. Chimeric antigen receptors (CAR) with modified thymus cells (T-cells) showed greater potential as a therapy due to its direct effect on immune system responsible for destruction of pathogens and said equivalent to the living drug. On activation of T-cell, it binds to the antigen domains treating refractory or relapsed cancers. The receptors are termed chimeric as it consists of T-cells functioning as well as antigen-binding combined in sole receptor. This therapy showed positive success towards hematological cancers and engineered for specific protein targeting. Though the therapy is associated to several challenges like incompetence towards tumor lysis and cytokine release rate, termination of cytotoxic activity after completion of tumor eradication, etc. The control mechanisms used by CAR T-cells are apoptosis by suicide genes, dual-antigen receptor, ON-switch tumor attack and bispecific molecules as activation switch. In solid tumors, CAR T-cell therapy showed promising signs of efficacy becoming a game-
D. Desai, R. S. Gaud, and P. Shende (*) Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM’S NMIMS, Mumbai, India e-mail: [email protected]
changing cell therapy. CAR T-cells are optimized using different engineering resolutions and lead to broadways for therapy adoption to benefit the cancer patients. Keywords
Antigen · Domain · Persistence · Receptor · Tumor
Abbreviations ABD ALL CAR GVHD ISD TAAs T-cells TD
1
Antigen-binding domain Acute lymphoblastic leukemia Chimeric antigen receptors Graft-versus-host disease Intracellular signaling domain Tumor-associated antigens Thymus cells Transmembrane domain
Introduction
Cancer is mainly treated with chemo- and radiation- therapies or combinational chemistry for target therapy but it causes cytotoxic effects and the rate of mortality depends on patient-related and technique-related factors like stages of cancer, patient age, patient history, cell engraftment,
D. Desai et al.
thymus cell (T-cell) cultivation, etc. To improve such treatment choices, various advance methods are developed like small molecular inhibitors, nanoparticulate-based therapies; laser treatment, monoclonal antibodies, etc. Among these, the first validated T-cell therapy in humans was used as a molecular remission induction technique in donor lymphocyte by infusion for treating myeloid malignancies. Later, it was clinically tested for Burkitt’s lymphoma, Hodgkin’s disease and nasopharyngeal carcinoma (Almåsbak et al. 2016; Mandpe et al. 2020; Patil et al. 2020; Shende et al. 2018; Deol and Lum 2010). Normal immune system cells, T-cells, use to fight against infections by killing cancerous cells or by directly attacking on viruses, bacteria and carcinoma using killer T-cells wher
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