Approaches for refining and furthering the development of CAR-based T cell therapies for solid malignancies

Caroline M. Hull, John Maher*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

4 Citations (Scopus)

Abstract

Introduction: Chimeric antigen receptor-engineered T-cells typically use the binding domains of antibodies to target cytotoxicity toward tumors. This approach has produced great efficacy against selected hematological cancers, but benefit in solid tumors has been limited. Characteristically, the microenvironment in solid tumors restricts CAR T cell function, thereby limiting success. Enhancing efficacy will depend on novel target discovery to refine specificity and reduce toxicity. Additionally, overcoming immunosuppressive mechanisms may be achieved by altering the structure of the CAR itself, together with ancillary gene expression or additional therapeutic interventions. Areas covered: Herein, the authors discuss approaches for refining and further developing CAR T cell therapies specifically for use with solid malignancies. The authors survey the existing literature and provide perspectives for the future. Expert opinion: Pronounced efficacy in solid tumors will likely require combination therapies, targeting both the tumor itself and associated immunosuppressive mechanisms. Future exploration of CAR T cell therapies for solid tumors is likely to incorporate next-generation designs that couple more precise targeting of cancer-associated targets with enhanced potency and resistance to exhaustion.

Original languageEnglish
Pages (from-to)1105-1117
Number of pages13
JournalExpert Opinion On Drug Discovery
Volume16
Issue number10
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • cancer
  • Car T cell
  • Chimeric antigen receptor
  • solid tumor

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