CAR T-cell Therapy: A New Era in Cancer Immunotherapy

Author(s): Androulla N. Miliotou, Lefkothea C. Papadopoulou*.

Journal Name: Current Pharmaceutical Biotechnology

Volume 19 , Issue 1 , 2018

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Abstract:

Background: Cancer is one of the leading causes of death worldwide. Over the years, a number of conventional cytotoxic approaches for neoplastic diseases has been developed. However, due to their limited effectiveness in accordance with the heterogeneity of cancer cells, there is a constant search for therapeutic approaches with improved outcome, such as immunotherapy that utilizes and enhances the normal capacity of the patient’s immune system.

Methods: Chimeric Antigen Receptor (CAR) T-cell therapy involves genetic modification of patient’s autologous T-cells to express a CAR specific for a tumor antigen, following by ex vivo cell expansion and re-infusion back to the patient. CARs are fusion proteins of a selected single-chain fragment variable from a specific monoclonal antibody and one or more T-cell receptor intracellular signaling domains. This T-cell genetic modification may occur either via viral-based gene transfer methods or nonviral methods, such as DNA-based transposons, CRISPR/Cas9 technology or direct transfer of in vitro transcribed-mRNA by electroporation.

Results: Clinical trials have shown very promising results in end-stage patients with a full recovery of up to 92% in Acute Lymphocytic Leukemia. Despite such results in hematological cancers, the effective translation of CAR T-cell therapy to solid tumors and the corresponding clinical experience is limited due to therapeutic barriers, like CAR T-cell expansion, persistence, trafficking, and fate within tumors.

Conclusion: In this review, the basic design of CARs, the main genetic modification strategies, the safety matters as well as the initial clinical experience with CAR T-cells are described.

Keywords: Cancer, immunotherapy, T-cell therapy, chimeric antigen receptor (CAR), genetic engineering, safety.

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Article Details

VOLUME: 19
ISSUE: 1
Year: 2018
Page: [5 - 18]
Pages: 14
DOI: 10.2174/1389201019666180418095526

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