Scholarlink

<p>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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年1月15日

查看全文
  • Stefano 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,
  • Michael Klichinsky

摘要

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.