CAR T cell therapy in solid tumors; with an extensive focus on obstacles and strategies to overcome the challenges

Int Immunopharmacol. 2021 Dec;101(Pt B):108260. doi: 10.1016/j.intimp.2021.108260. Epub 2021 Oct 19.


The application of the CAR T cell therapy in hematologic malignancies holds prosperous results that intensified the unprecedented enthusiasm to employ this fascinating strategy in other types of human malignancies. Although the researchers invested a great deal of effort to exploit the utmost efficacy of these cells in the context of solid tumors, few articles reviewed obstacles and opportunities. The current review aims to provide comprehensive literature of recent advances of CAR T cell therapy in a wide range of solid tumors; and also, to discuss the original data obtained from international research laboratories on this topic. Despite promising results, several radical obstacles are on the way of this approach. This review discusses the most important drawbacks and also responds to questions on how the intrinsic features of solid tumors in addition to the tumor microenvironment-related challenges and the immune-relating adverse effects can curb satisfactory outcomes of CAR T cells. The last section allocates a special focus on innovative and contemporary policies which have already been adopted to surmount these challenges. Finally, we comment on the future research aspects in which the efficacy, as well as the safety of CAR T cell therapy, might be improved.

Keywords: Adoptive cell therapy; CAR T cell; Cancer immunotherapy; Chimeric antigen receptor; Solid tumor; Tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Animals
  • Cancer Vaccines / immunology*
  • Humans
  • Immunotherapy, Adoptive / adverse effects
  • Immunotherapy, Adoptive / methods*
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Receptors, Chimeric Antigen / genetics
  • Tumor Microenvironment


  • Cancer Vaccines
  • Receptors, Chimeric Antigen