Small-Molecule Compounds Boost CAR-T Cell Therapy in Hematological Malignancies

Curr Treat Options Oncol. 2023 Mar;24(3):184-211. doi: 10.1007/s11864-023-01049-4. Epub 2023 Jan 26.

Abstract

Although chimeric antigen receptor T cell immunotherapy has been successfully applied in patients with hematological malignancies, several obstacles still need to be overcome, such as high relapse rates and side effects. Overcoming the limitations of CAR-T cell therapy and boosting the efficacy of CAR-T cell therapy are urgent issues that must be addressed. The exploration of small-molecule compounds in combination with CAR-T cell therapies has achieved promising success in pre-clinical and clinical studies in recent years. Protein kinase inhibitors, demethylating drugs, HDAC inhibitors, PI3K inhibitors, immunomodulatory drugs, Akt inhibitors, mTOR inhibitors, and Bcl-2 inhibitors exhibited potential synergy in combination with CAR-T cell therapy. In this review, we will discuss the recent application of these combination therapies for improved outcomes of CAR-T cell therapy.

Keywords: Chimeric antigen receptor T cells; Hematological malignancies; Small-molecule compounds.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell- and Tissue-Based Therapy
  • Hematologic Neoplasms* / therapy
  • Humans
  • Immunotherapy, Adoptive / adverse effects
  • Phosphatidylinositol 3-Kinases
  • Protein Kinase Inhibitors
  • Receptors, Chimeric Antigen*

Substances

  • Phosphatidylinositol 3-Kinases
  • Receptors, Chimeric Antigen
  • Protein Kinase Inhibitors