TriBAFF-CAR-T Cells Eliminate B-cell Malignancies with BAFFR-expression and CD19 Antigen Loss

Overview

Journal Cancer Cell Int

Publisher Biomed Central

Date 2021 Apr 18

PMID 33865370

Citations 2

Authors

Guangchao Li

Qing Zhang

Zhi Liu

Huijuan Shen

Yangmin Zhu

Zhao Zhou

Wen Ding

Siqi Han

Jie Zhou

Ruiming Ou

Min Luo

Shuang Liu

Affiliations

Soon will be listed here.

Abstract

Background: To investigate the effect of TriBAFF-CAR-T cells on hematological tumor cells.

Methods: TriBAFF-CAR-T and CD19-CAR-T cells were co-cultured with BAFFR-bearing B-cell malignancies at different effector/target ratios to evaluate the anti-tumor effects. In vivo, TriBAFF-CAR-T and CD19-CAR-T cells were intravenously injected into Raji-luciferase xenograft mice. CD19 antigens losing lymphoblasts was simulated by Raji knocking out CD19 (CD19) to investigate the effect of TriBAFF-CAR-T cells on CD19 Raji.

Results: Both TriBAFF-CAR-T and CD19-CAR-T cells significantly induced the lysis of Raji, BALL-1, and Jeko-1. Moreover, when CD19-CAR-T cells specifically caused the lysis of K562 with overexpressed CD19, the lethal effect of TriBAFF-CAR-T cells was also specific for BAFFR-bearing K562 with increasing levels of interleukin-2 and INF-γ. The TriBAFF-CAR-T have the same effect with CD19-CAR-T cells in treating Raji xenofraft mice. TriBAFF-CAR-T cells also have great effect in CD19 Raji cells.

Conclusions: In this study, we successfully constructed novel TriBAFF-CAR-T cells to eliminate BAFFR-bearing and CD19 antigen loss in hematological tumor cells.

Citing Articles

Split-design approach enhances the therapeutic efficacy of ligand-based CAR-T cells against multiple B-cell malignancies.

Li S, Shi L, Zhao L, Guo Q, Li J, Liu Z Nat Commun. 2024; 15(1):9751.

PMID: 39528513 PMC: 11555413. DOI: 10.1038/s41467-024-54150-z.

Both APRIL and antibody-fragment-based CAR T cells for myeloma induce BCMA downmodulation by trogocytosis and internalization.

Camviel N, Wolf B, Croce G, Gfeller D, Zoete V, Arber C J Immunother Cancer. 2022; 10(11).

PMID: 36323436 PMC: 9639149. DOI: 10.1136/jitc-2022-005091.

References

Jensen M, Riddell S . Design and implementation of adoptive therapy with chimeric antigen receptor-modified T cells. Immunol Rev. 2013; 257(1):127-44. PMC: 3991306. DOI: 10.1111/imr.12139. View

Yang S, Li J, Xu W . Role of BAFF/BAFF-R axis in B-cell non-Hodgkin lymphoma. Crit Rev Oncol Hematol. 2014; 91(2):113-22. DOI: 10.1016/j.critrevonc.2014.02.004. View

Du J, Zhang Y . Sequential anti-CD19, 22, and 20 autologous chimeric antigen receptor T-cell (CAR-T) treatments of a child with relapsed refractory Burkitt lymphoma: a case report and literature review. J Cancer Res Clin Oncol. 2020; 146(6):1575-1582. DOI: 10.1007/s00432-020-03198-7. View

Mihalcik S, Tschumper R, Jelinek D . Transcriptional and post-transcriptional mechanisms of BAFF-receptor dysregulation in human B lineage malignancies. Cell Cycle. 2010; 9(24):4884-92. PMC: 3047811. DOI: 10.4161/cc.9.24.14156. View

Shin W, Lee H, Lim H, Lee S, Son J, Lee J . BAFF-neutralizing interaction of belimumab related to its therapeutic efficacy for treating systemic lupus erythematosus. Nat Commun. 2018; 9(1):1200. PMC: 5865148. DOI: 10.1038/s41467-018-03620-2. View

Watanabe K, Terakura S, Martens A, van Meerten T, Uchiyama S, Imai M . Target antigen density governs the efficacy of anti-CD20-CD28-CD3 ζ chimeric antigen receptor-modified effector CD8+ T cells. J Immunol. 2014; 194(3):911-20. DOI: 10.4049/jimmunol.1402346. View

Qin H, Dong Z, Wang X, Cheng W, Wen F, Xue W . CAR T cells targeting BAFF-R can overcome CD19 antigen loss in B cell malignancies. Sci Transl Med. 2019; 11(511). PMC: 7015136. DOI: 10.1126/scitranslmed.aaw9414. View

Shabgah A, Shariati-Sarabi Z, Tavakkol-Afshari J, Mohammadi M . The role of BAFF and APRIL in rheumatoid arthritis. J Cell Physiol. 2019; 234(10):17050-17063. DOI: 10.1002/jcp.28445. View

Smulski C, Eibel H . BAFF and BAFF-Receptor in B Cell Selection and Survival. Front Immunol. 2018; 9:2285. PMC: 6186824. DOI: 10.3389/fimmu.2018.02285. View

10.

Neelapu S, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke F . Chimeric antigen receptor T-cell therapy - assessment and management of toxicities. Nat Rev Clin Oncol. 2017; 15(1):47-62. PMC: 6733403. DOI: 10.1038/nrclinonc.2017.148. View

11.

Fesnak A, Lin C, Siegel D, Maus M . CAR-T Cell Therapies From the Transfusion Medicine Perspective. Transfus Med Rev. 2016; 30(3):139-45. PMC: 4914456. DOI: 10.1016/j.tmrv.2016.03.001. View

12.

Sotillo E, Barrett D, Black K, Bagashev A, Oldridge D, Wu G . Convergence of Acquired Mutations and Alternative Splicing of CD19 Enables Resistance to CART-19 Immunotherapy. Cancer Discov. 2015; 5(12):1282-95. PMC: 4670800. DOI: 10.1158/2159-8290.CD-15-1020. View

13.

Vincent F, Saulep-Easton D, Figgett W, Fairfax K, Mackay F . The BAFF/APRIL system: emerging functions beyond B cell biology and autoimmunity. Cytokine Growth Factor Rev. 2013; 24(3):203-15. PMC: 7108297. DOI: 10.1016/j.cytogfr.2013.04.003. View

14.

Wei G, Wang J, Huang H, Zhao Y . Novel immunotherapies for adult patients with B-lineage acute lymphoblastic leukemia. J Hematol Oncol. 2017; 10(1):150. PMC: 5563021. DOI: 10.1186/s13045-017-0516-x. View

15.

Ruella M, Barrett D, Kenderian S, Shestova O, Hofmann T, Perazzelli J . Dual CD19 and CD123 targeting prevents antigen-loss relapses after CD19-directed immunotherapies. J Clin Invest. 2016; 126(10):3814-3826. PMC: 5096828. DOI: 10.1172/JCI87366. View

16.

Porter D, Levine B, Kalos M, Bagg A, June C . Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med. 2011; 365(8):725-33. PMC: 3387277. DOI: 10.1056/NEJMoa1103849. View

17.

Hildebrand J, Luo Z, Manske M, Price-Troska T, Ziesmer S, Lin W . A BAFF-R mutation associated with non-Hodgkin lymphoma alters TRAF recruitment and reveals new insights into BAFF-R signaling. J Exp Med. 2010; 207(12):2569-79. PMC: 2989778. DOI: 10.1084/jem.20100857. View

18.

Maus M, Haas A, Beatty G, Albelda S, Levine B, Liu X . T cells expressing chimeric antigen receptors can cause anaphylaxis in humans. Cancer Immunol Res. 2014; 1(1):26-31. PMC: 3888798. DOI: 10.1158/2326-6066.CIR-13-0006. View

19.

Kochenderfer J, Yu Z, Frasheri D, Restifo N, Rosenberg S . Adoptive transfer of syngeneic T cells transduced with a chimeric antigen receptor that recognizes murine CD19 can eradicate lymphoma and normal B cells. Blood. 2010; 116(19):3875-86. PMC: 2981541. DOI: 10.1182/blood-2010-01-265041. View

20.

Yang F, Zhang J, Zhang X, Tian M, Wang J, Kang L . Delayed remission following sequential infusion of humanized CD19- and CD22-modified CAR-T cells in a patient with relapsed/refractory acute lymphoblastic leukemia and prior exposure to murine-derived CD19-directed CAR-T cells. Onco Targets Ther. 2019; 12:2187-2191. PMC: 6438143. DOI: 10.2147/OTT.S189103. View