Clinical & Translational Immunology (Jan 2022)

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

  • Kevin P Nishimoto,
  • Taylor Barca,
  • Aruna Azameera,
  • Amani Makkouk,
  • Jason M Romero,
  • Lu Bai,
  • Mary M Brodey,
  • Jackie Kennedy‐Wilde,
  • Hui Shao,
  • Stephanie Papaioannou,
  • Amy Doan,
  • Cynthia Masri,
  • Ngoc T Hoang,
  • Hayden Tessman,
  • Vidhya Dhevi Ramanathan,
  • Ana Giner‐Rubio,
  • Frank Delfino,
  • Kriti Sharma,
  • Kevin Bray,
  • Matthew Hoopes,
  • Daulet Satpayev,
  • Ranjita Sengupta,
  • Marissa Herrman,
  • Stewart E Abbot,
  • Blake T Aftab,
  • Zili An,
  • Swapna Panuganti,
  • Sandra M Hayes

DOI
https://doi.org/10.1002/cti2.1373
Journal volume & issue
Vol. 11, no. 2
pp. n/a – n/a

Abstract

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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).

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