Stem Cell Reviews and Reports

, Volume 15, Issue 5, pp 619–636 | Cite as

Solid Tumors Challenges and New Insights of CAR T Cell Engineering

  • Safa Tahmasebi
  • Reza Elahi
  • Abdolreza EsmaeilzadehEmail author


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.


Immunotherapy Adoptive cell therapy Challenges Solid tumor Chimeric antigen receptor CAR T cell 


Author Contributions

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.

Funding Resources

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Safa Tahmasebi
    • 1
  • Reza Elahi
    • 2
  • Abdolreza Esmaeilzadeh
    • 3
    • 4
    Email author
  1. 1.Department of Immunology, Health FacultyTehran University of Medical SciencesTehranIran
  2. 2.School of MedicineZanjan University of Medical SciencesZanjanIran
  3. 3.Department of ImmunologyZanjan University of Medical ScienceZanjanIran
  4. 4.Cancer Gene Therapy Research CenterZanjan University of Medical ScienceZanjanIran

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