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Solid Tumors Challenges and New Insights of CAR T Cell Engineering

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Abstract

Adoptive cell therapy using CAR T cells has emerged as a novel treatment strategy with promising results against B cell malignancies; however, CAR T cells have not shown much success against solid malignancies. There are several obstacles which diminish the efficacy of CAR T cells, but the immunosuppressive tumor microenvironment (TME) of the tumor stands out as the most important factor. TME includes Tumor-Associated Stroma, Immunosuppressive cells and cytokines, tumor hypoxia and metabolism, and Immune Inhibitory Checkpoints which affect the CAR T cell efficacy and activity in solid tumors. A precise understanding of the TME could pave the way to engineer novel modifications of CAR T cells which can overcome the immunosuppressive TME. In this review, we will describe different sections of the TME and introduce novel approaches to improve the CAR T cells potential against solid tumors based on recent clinical and preclinical data. Also, we will provide new suggestions on how to modify CARs to augment of CAR T cells efficacy. Since there are also some challenges beyond the TME that are important for CAR function, we will also discuss and provide data about the improvement of CAR T cells trafficking and delivery to the tumor site and how to solve the problem of tumor antigen heterogeneity.

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Authors and Affiliations

  1. Department of Immunology, Health Faculty, Tehran University of Medical Sciences, Tehran, Iran

    Safa Tahmasebi

  2. School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran

    Reza Elahi

  3. Department of Immunology, Zanjan University of Medical Science, Zanjan, Iran

    Abdolreza Esmaeilzadeh

  4. Cancer Gene Therapy Research Center, Zanjan University of Medical Science, Zanjan, Iran

    Abdolreza Esmaeilzadeh

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ST and RE contributed to data gathering, writing the primary draft of the manuscript, and designing figures and Tables. AE contributed to the hypothesis, corresponding, scientific and structural editing, and verifying the manuscript before submission.

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Correspondence to Abdolreza Esmaeilzadeh.

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Tahmasebi, S., Elahi, R. & Esmaeilzadeh, A. Solid Tumors Challenges and New Insights of CAR T Cell Engineering. Stem Cell Rev and Rep 15, 619–636 (2019). https://doi.org/10.1007/s12015-019-09901-7

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  • DOI: https://doi.org/10.1007/s12015-019-09901-7

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