ADI-270: an armored allogeneic gamma delta T cell therapy designed to target CD70-expressing solid and hematologic malignancies

作者：Kevin Nishimoto, Gauri Lamture, Yvan H. Chanthery, Alexander Teague, Yogendra Verma, Melinda Au, Morgan Smith‐Boeck, Michael Salum, Pranav Murthy, Smitha Gundurao, Ramandeep Kaur, Jie Zhang, Aruna Azameera, Jonathan T S Wong, Elizabeth Speltz, Katherine Wang, Amy Doan, Jyothi Sethuraman, Dishant Bhatwala, Ana Giner‐Rubio, Pavan Puligujja, Helen Budworth, Christopher J. Rold, Swapna Panuganti, Aya Jakobovits, Marissa Herrman, Arun Bhat, Shon Green, Blake T. Aftab · 发表于：Journal for ImmunoTherapy of Cancer · 年份：2025 · DOI：10.1136/jitc-2025-011704 · 被引用次数：14 · 研究领域：CAR-T cell therapy research、Monoclonal and Polyclonal Antibodies Research、Immunotherapy and Immune Responses

Background The tumor microenvironment (TME) poses challenges that limit the efficacy of conventional CAR-T cell therapies. Homing barriers, immunosuppressive factors, and target antigen heterogeneity can impair CAR-T cell functional activity within the TME. Alternative strategies have contemplated incorporating the use of gamma delta (γδ) T cells as a CAR-T cell approach to potentially overcome these limitations. γδ T cells possess both innate and adaptive immunity to facilitate broad tumor recognition, and their natural propensity for tissue tropism may allow for more effective tumor infiltration. Reported here is the preclinical characterization of ADI-270, an allogeneic γδ CAR-T cell product targeting CD70 + cancers, engineered with a third-generation CAR based on the natural CD27 receptor. ADI-270 is also double-armored to mitigate the immunosuppressive effects of TGFβ and reduce the potential for allogeneic rejection. Methods Vδ1 T cells engineered to express an anti-CD70 CAR and dominant negative TGFβ receptor II (dnTGFβRII) were expanded from healthy donor human PBMCs. The phenotype and functional characterization of ADI-270 were assessed with in vitro cell culture assays and in vivo tumor xenograft models. Results ADI-270 exhibited high levels of in vitro cytotoxicity against a panel of cancer cell lines and displayed a favorable inflammatory cytokine profile compared with reference scFv-based anti-CD70 CAR αβ T cells. Cytotoxicity remained potent despite low CD70 exp...