Resistance to CART cell therapy: lessons learned from the treatment of hematological malignancies

Reona Sakemura, Michelle J. Cox, Mehrdad Hefazi, Elizabeth L. Siegler, Saad S. Kenderian

Research output: Contribution to journalReview articlepeer-review

Abstract

Chimeric antigen receptor T (CART) cell immunotherapy has yielded significant clinical success in treating certain hematological malignancies. However, despite high initial response rates, most patients eventually relapse. Resistance to CART cell therapy can stem from tumor cell mutations, T cell defects, and tumor microenvironment (TME) immunosuppression. Tumor cells can downregulate target antigen expression to evade CART cell detection or mutate death receptor pathways to resist CART cell cytotoxicity. Patient T cells can be intrinsically defective, and CART cells often undergo exhaustion. The TME is abundant with immunosuppressive cells and factors which contribute to suboptimal CART cell activity. Collectively, issues originating in tumor cells, T cells, and the TME present significant hurdles to long-term remission after CART cell therapy. Various strategies to combat CART cell resistance have shown promise in preclinical studies and early clinical trials and are crucial to achieving durable responses.

Original languageEnglish (US)
JournalLeukemia and Lymphoma
DOIs
StateAccepted/In press - 2021

Keywords

  • CART
  • drug resistance
  • mechanism
  • treatment

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Resistance to CART cell therapy: lessons learned from the treatment of hematological malignancies'. Together they form a unique fingerprint.

Cite this