Programmable and multi-targeted CARs: a new breakthrough in cancer CAR-T cell therapy
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REVIEW ARTICLE
Programmable and multi‑targeted CARs: a new breakthrough in cancer CAR‑T cell therapy S. Tahmasebi1 · R. Elahi2 · E. Khosh2 · A. Esmaeilzadeh3,4,5 Received: 27 June 2020 / Accepted: 31 August 2020 © Federación de Sociedades Españolas de Oncología (FESEO) 2020
Abstract CAR-T cell therapy, as a novel immunotherapy approach, has indicated successful results in the treatment of hematological malignancies; however, distinct results have been achieved regarding solid tumors. Tumor immunosuppressive microenvironment has been identified as the most critical barrier in CAR-T cell therapy of solid tumors. Developing novel strategies to augment the safety and efficacy of CAR-T cells could be useful to overcome the solid tumor hurdles. Similar to other cancer treatments, CAR-T cell therapy can cause some side effects, which can disturb the healthy tissues. In the current review, we will discuss the practical breakthroughs in CAR-T cell therapy using the multi-targeted and programmable CARs instead of conventional types. These superior types of CAR-T cells have been developed to increase the function and safety of T cells in a controllable manner, which would diminish the incidence of relevant side effects. Moreover, we will describe the capability of these powerful CARs in targeting multiple tumor antigens, redirecting the CAR-T cells to specific target cells, incrementing the safety of CARs, and other advantages that lead to promising outcomes in cancer CAR-T cell therapy. Keywords Adoptive cell therapy · Conventional CARs · Multi-targeted CARs · Programmable CARs · Cancer · Immunotherapy
Introduction Cancer is one of the most substantial causes of death worldwide, with several unknown complex mechanisms that usually lead to treatment failure. In recent years, immunotherapy approaches based on immune system responses appeared as novel cancer therapeutic strategies, which have taken substantial strides forward in improving the success rate of treatments in malignancies [1]. Immunotherapy regimens are including monoclonal antibodies (mAbs), checkpoint * A. Esmaeilzadeh [email protected] 1
Department of Immunology, Health Faculty, Tehran University of Medical Sciences, Tehran, Iran
2
School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
3
Department of Immunology, Zanjan University of Medical Science, Zanjan, Iran
4
Cancer Gene Therapy Research Center, Zanjan University of Medical Science, Zanjan, Iran
5
Immunotherapy Research and Technology Group, Zanjan University of Medical Science, Zanjan, Iran
inhibitors, anti-cancer vaccines, cytokine therapy, oncolytic virus therapy, and adoptive cell therapy (ACT) [2]. Adoptive cell therapy has been developed to target the tumor cells using the patient’s immune cells after ex-vivo engineering and expansion [3]. During recent years, chimeric antigen receptor (CAR) T cell therapy, an effective and novel ACT therapy, has emerged as a breakthrough in treating the various immunological disorders, such as hematological and solid cancers
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