CAR-T Cell Therapy: Genetically engineered T cell as a new era in immunotherapy to treat cancer Rochana Pramanik, M.Sc Student, Department of Physiology, University of Calcutta Background Cancer is one of the leading causes of death worldwide. For years, the foundation of cancer treatment were surgery, chemotherapy and radiation therapy. Over the last two decades, targeted therapies cemented themselves as standard treatment for many cancers. Due to the limited effectiveness owing to the heterogeneity of different types of cancer there has been a constant search for novel therapeutic approaches with improved outcome, such as immunotherapy that utilizes and strengthens the normal capacity of the immune system. Over the past several years, it emerged as the 'fifth pillar' of cancer treatment.
Results Clinical trials show high success rates in end-stage patients with full recovery upto 92% in acute lymphocytic leukemia. Despite such promising results in haematological cancers, CAR T cell therapy shows limitation in effective translation in case of solid tumours and clinical experience due to therapeutic barriers like T cell expansion, persistence and trafficking.
Conclusion The basic design, methodologies for genetic modification and safety matters with CAR T cells are described. This therapy has the future potential to bring a breakthrough in cancer treatment strategy.
Methods The most common procedure for CAR T cell therapy involves the extraction of T cells from the patient's blood called leukapheresis, followed by genetic modification to express a Chimeric antigen receptor (CAR) on its surface specific for a tumour antigen, which is brought about by viral-based gene transfer or non-viral methods such as, DNA-based transposons, CRISPR-Cas 9 technology, or direct transfer of in-vitro transcribed m-RNA by electroporation. The CAR T cells are cultured for ex-vivo cell expansion followed by re-infusion to the patient to attack cancer cells. CARs are fusion proteins of selected single chain fragments from a specific monoclonal antibody and one or more T cell receptor intracellular signalling domain.
Future applications of chimeric antigen receptor T cell therapy or chimeric autoantibody receptor T cell treatment. Solid arrows indicate indications under clinical trial or preclinical trials. Dotted arrows depict expandable human disease by CAR T or CAAR T therapy, respectively. HCC: hepatocellular carcinoma, IPF: idiopathic pulmonary fibrosis, PKD: polycystic kidney disease, SLE: systemic lupus erythematosus.
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CAR T cells and TCR T cells are engineered to produce special receptors on their surfaces. They are then expanded in the laboratory and returned to the patient. Credit: National Cancer Institute-
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