Chimeric antigen receptor macrophages (CAR-M) sensitize HER2+ solid tumors to PD1 blockade in pre-clinical models.

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Tác giả: Sascha Abramson, Michael Ball, Daniel Blumenthal, Sabrina Ceeraz DeLong, Sotheavy Chhum, Kerri Ciccaglione, Thomas Condamine, Linara Cornell, Daniel Cushing, Rashid Gabbasov, Saar Gill, Crystal Griffin, Shuo Huang, Michael Klichinsky, Hyam Levitsky, Lurong Lian, Nicholas Minutolo, Karan Nagar, Maria Cecilia Oliveira-Nunes, Stefano Pierini, Rehman Qureshi, Kayleigh Ross, Benjamin Schott, Lauren Shaw, Olga Shestova, Christopher Sloas, Poonam Sonawane, Bindu Varghese, Alison Worth, Yumi Yashiro-Ohtani, Isaac Zentner

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: England : Nature communications , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 720818

We previously developed human CAR macrophages (CAR-M) and demonstrated redirection of macrophage anti-tumor function leading to tumor control in immunodeficient xenograft models. Here, we develop clinically relevant fully immunocompetent syngeneic models to evaluate the potential for CAR-M to remodel the tumor microenvironment (TME), induce T cell anti-tumor immunity, and sensitize solid tumors to PD1/PDL1 checkpoint inhibition. In vivo, anti-HER2 CAR-M significantly reduce tumor burden, prolong survival, remodel the TME, increase intratumoral T cell and natural killer (NK) cell infiltration, and induce antigen spreading. CAR-M therapy protects against antigen-negative relapses in a T cell dependent fashion, confirming long-term anti-tumor immunity. In HER2+ solid tumors with limited sensitivity to anti-PD1 (aPD1) monotherapy, the combination of CAR-M and aPD1 significantly improves tumor growth control, survival, and remodeling of the TME in pre-clinical models. These results demonstrate synergy between CAR-M and T cell checkpoint blockade and provide a strategy to potentially enhance response to aPD1 therapy for patients with non-responsive tumors.
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