A second-generation CD38-CAR-T cell for the treatment of multiple myeloma

Cancer Med. 2023 May;12(9):10804-10815. doi: 10.1002/cam4.5818. Epub 2023 Apr 11.

Abstract

Background: Multiple myeloma (MM) is an aggressive plasma cell malignancy, causing a number of deaths worldwide every year. Chimeric antigen receptor (CAR) transduced T-cell therapy has been a promising immunotherapy against hematological malignancies.

Methods: In this study, we developed a second-generation CAR construct and generated CAR-T cells targeting CD38 molecule. Then effects of CAR-T cells against MM cell lines were evaluated.

Results: CD38-CAR-T cells showed higher cytotoxicity to MM cell lines and primary MM cells than that of control T cells in vitro. Over 50% MM1.s and RPMI8226 cells were killed by CAR-T cells even at effector to target ratio of 1:100. CAR-T cells also showed an enhanced cytotoxicity against primary MM cells. CAR-T cells could be activated and produced a variety of cytokines in a target-dependent manner. In vivo test indicated that CAR-T cells also showed significant antitumor effect on xenograft mice models.

Conclusion: These results indicated a promising therapeutic strategy of CD38-CAR-T cells against MM.

Keywords: CD38; chimeric antigen receptor; immunotherapy; multiple myeloma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Humans
  • Immunotherapy / methods
  • Immunotherapy, Adoptive
  • Mice
  • Multiple Myeloma* / pathology
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Chimeric Antigen* / genetics
  • Receptors, Chimeric Antigen* / metabolism
  • T-Lymphocytes
  • Xenograft Model Antitumor Assays

Substances

  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen