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

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:

• CAR-T cells
• B-cell malignant tumors
• CD19
• CD22

Ethical approval and consent to participate

The experimental protocol used in this study was approved by the Animal Care and Use Committee of the Yongnuo Medical Laboratory Animal Center (No. 2018-0186).

Author contributions

Conception and design of the research: SL, LL, and PZ; acquisition of data: WZ, QZ, YZ, LP, BW, HS, and ZL; analysis and interpretation of data: LP, BW, HS, and ZL; statistical analysis: LP, BW, HS, and ZL; obtaining funding: SL, LL, and PZ; drafting the manuscript: WZ, QZ, YZ, and RO; revision of the manuscript for important intellectual content: SL, LL, and PZ. All authors read and approved the final manuscript.

Declaration of interest

The authors declare that they have no competing interest.

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This study was supported by the Guangzhou Science and Technology Plan Project [202002030404], the Foundation of Guangdong Second Provincial General Hospital [2017-001, 3DB2020014, YQ2020-002], Doctoral Workstation Foundation of Guangdong Second Provincial General Hospital [2019BSGZ008, 2020BSGZ048, 2021BSGZ017], Guangdong Medical Scientific Research [B2020092]; Natural Science Foundation of Guangdong Province [2021A1515012329] and Foundation of Deyang People’s Hospital [FHT202004].