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

同种异体 CD20 靶向 γδ T 细胞在临床前 B 细胞淋巴瘤模型中表现出先天和适应性抗肿瘤活性

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作者: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, Matt

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).

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.

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