Open AccessAllogeneic CD20‐targeted γδ T cells exhibit innate and adaptive antitumor activities in preclinical B‐cell lymphoma models
Author(s) -
Nishimoto Kevin P,
Barca Taylor,
Azameera Aruna,
Makkouk Amani,
Romero Jason M,
Bai Lu,
Brodey Mary M,
KennedyWilde Jackie,
Shao Hui,
Papaioannou Stephanie,
Doan Amy,
Masri Cynthia,
Hoang Ngoc T,
Tessman Hayden,
Ramanathan Vidhya Dhevi,
GinerRubio Ana,
Delfino Frank,
Sharma Kriti,
Bray Kevin,
Hoopes Matthew,
Satpayev Daulet,
Sengupta Ranjita,
Herrman Marissa,
Abbot Stewart E,
Aftab Blake T,
An Zili,
Panuganti Swapna,
Hayes Sandra M
Publication year - 2022
Publication title -
clinical and translational immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.321
H-Index - 34
ISSN - 2050-0068
DOI - 10.1002/cti2.1373
Subject(s) - cd20 , chimeric antigen receptor , immunology , cancer research , medicine , cytotoxic t cell , t cell , ex vivo , b cell , lymphoma , in vivo , biology , immune system , in vitro , antibody , biochemistry , microbiology and biotechnology
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).