Engineering Novel CD19/CD22 Dual-Target CAR-T Cells for Improved Anti-Tumor Activity

Cancer Invest. 2022 Mar;40(3):282-292. doi: 10.1080/07357907.2021.2005798. Epub 2021 Nov 25.

Abstract

Despite high remission rates following chimeric antigen receptor T cell (CAR-T) cell therapy in B-cell acute lymphoblastic leukemia (B-ALL), relapse due to loss of the targeted antigen is increasingly recognized as a mechanism of immune escape. We hypothesized that simultaneous targeting of CD19 and CD22 may improve the CAR-T effect. The in vitro and in vivo leukemia model was established, and the anti-tumor effects of BiCAR-T, CD19 CAR-T, CD22 CAR-T, and LoopCAR6 cells were observed. We found that the BiCAR-T cells showed significant cytotoxicity in vitro and in vivo. The CD19/CD22 bivalent CAR provides an opportunity to test whether simultaneous targeting may reduce the risk of antigen loss.

Keywords: B-cell malignant tumors; CAR-T cells; CD19; CD22.

MeSH terms

  • Animals
  • Antigens, CD19 / genetics
  • Antigens, CD19 / immunology*
  • Female
  • Humans
  • Immunotherapy, Adoptive / methods*
  • K562 Cells
  • Lentivirus / genetics
  • Leukemia, Experimental / therapy*
  • Mice
  • Receptors, Chimeric Antigen / immunology*
  • Sialic Acid Binding Ig-like Lectin 2 / genetics
  • Sialic Acid Binding Ig-like Lectin 2 / immunology*

Substances

  • Antigens, CD19
  • CD19 molecule, human
  • CD22 protein, human
  • Receptors, Chimeric Antigen
  • Sialic Acid Binding Ig-like Lectin 2