Allogeneic CD20‐targeted γδ T cells exhibit innate and adaptive antitumor activities in preclinical B‐cell lymphoma models

Clinical & Translational Immunology

Kevin P Nishimoto¹  Taylor Barca¹  Ana Giner‐Rubio¹  Stewart E Abbot¹  Ranjita Sengupta¹  Jackie Kennedy‐Wilde¹  Blake T Aftab¹  Ngoc T Hoang¹  Amy Doan¹  Hayden Tessman¹  Mary M Brodey¹  Cynthia Masri¹  Lu Bai¹  Hui Shao¹  Swapna Panuganti¹  Aruna Azameera¹  Sandra M Hayes¹  Amani Makkouk¹  Daulet Satpayev¹  Marissa Herrman¹  Stephanie Papaioannou¹  Vidhya Dhevi Ramanathan¹  Jason M Romero¹  Matthew Hoopes¹  Zili An¹  Kriti Sharma²  Frank Delfino²  Kevin Bray² 

[1] Adicet Bio, Inc. Menlo Park CA USA;Regeneron Pharmaceuticals, Inc. Tarrytown NY USA;

关键词: adoptive cell therapy;    B‐cell lymphoma;    CD20;    chimeric antigen receptor;    γδ T cells;   

DOI  :  10.1002/cti2.1373

来源: DOAJ

【 摘 要 】

Abstract Objectives Autologous chimeric antigen receptor (CAR) αβ T‐cell therapies have demonstrated remarkable antitumor efficacy in patients with haematological malignancies; however, not all eligible cancer patients receive clinical benefit. Emerging strategies to improve patient access and clinical responses include using premanufactured products from healthy donors and alternative cytotoxic effectors possessing intrinsic tumoricidal activity as sources of CAR cell therapies. γδ T cells, which combine innate and adaptive mechanisms to recognise and kill malignant cells, are an attractive candidate platform for allogeneic CAR T‐cell therapy. Here, we evaluated the manufacturability and functionality of allogeneic peripheral blood‐derived CAR+ Vδ1 γδ T cells expressing a second‐generation CAR targeting the B‐cell‐restricted CD20 antigen. Methods Donor‐derived Vδ1 γδ T cells from peripheral blood were ex vivo‐activated, expanded and engineered to express a novel anti‐CD20 CAR. In vitro and in vivo assays were used to evaluate CAR‐dependent and CAR‐independent antitumor activities of CD20 CAR+ Vδ1 γδ T cells against B‐cell tumors. Results Anti‐CD20 CAR+ Vδ1 γδ T cells exhibited innate and adaptive antitumor activities, such as in vitro tumor cell killing and proinflammatory cytokine production, in addition to in vivo tumor growth inhibition of B‐cell lymphoma xenografts in immunodeficient mice. Furthermore, CD20 CAR+ Vδ1 γδ T cells did not induce xenogeneic graft‐versus‐host disease in immunodeficient mice. Conclusion These preclinical data support the clinical evaluation of ADI‐001, an allogeneic CD20 CAR+ Vδ1 γδ T cell, and a phase 1 study has been initiated in patients with B‐cell malignancies (NCT04735471).

【 授权许可】

Unknown