 Chimeric antigen receptor macrophages (CAR-M) sensitize HER2+ solid tumors to PD1 blockade in pre-clinical modelsStefano Pierini,
Rashid Gabbasov,
Maria Cecilia Oliveira-Nunes,
Rehman Qureshi,
Alison Worth,
Shuo Huang,
Karan Nagar,
Crystal Griffin,
Lurong Lian,
Yumi Yashiro-Ohtani,
Kayleigh Ross,
Christopher Sloas,
Michael Ball,
Benjamin Schott,
Poonam Sonawane,
Linara Cornell,
Daniel Blumenthal,
Sotheavy Chhum,
Nicholas Minutolo,
Kerri Ciccaglione,
Lauren Shaw,
Isaac Zentner,
Hyam Levitsky,
Olga Shestova,
Saar Gill,
Bindu Varghese,
Daniel Cushing,
Sabrina Ceeraz DeLong,
Sascha Abramson,
Thomas Condamine and
Michael Klichinsky ()
Nature Communications, 2025, vol. 16, issue 1, 1-16 Abstract: Abstract 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. Date: 2025 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-024-55770-1 Ordering information: This journal article can be ordered from DOI: 10.1038/s41467-024-55770-1 Access Statistics for this article Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie More articles in Nature Communications from Nature |
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