Biomedicine & Pharmacotherapy (Aug 2024)

Engineering M1 macrophages with targeting aptamers for enhanced adoptive immunotherapy by modifying the cell surface

  • Qian Yang,
  • Shiyi Hu,
  • Yiqiu Wang,
  • Luyi Zhong,
  • Xiaoli Yu,
  • Yifeng Zhang,
  • Xiao Du,
  • Shuling Wang,
  • Qingchang Tian

Journal volume & issue
Vol. 177
p. 117064

Abstract

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Macrophages play a critical role in the body's defense against cancer by phagocytosing tumor cells, presenting antigens, and activating adaptive T cells. However, macrophages are intrinsically incapable of delivering targeted cancer immunotherapies. Engineered adoptive cell therapy introduces new targeting and antitumor capabilities by modifying macrophages to enhance the innate immune response of cells and improve clinical efficacy. In this study, we developed engineered macrophage cholesterol-AS1411-M1 (CAM1) for cellular immunotherapy. To target macrophages, cholesterol-AS1411 aptamers were anchored to the surface of M1 macrophages to produce CAM1 without genetic modification or cell damage. CAM1 induced significantly higher apoptosis/mortality than unmodified M1 macrophages in murine breast cancer cells. Anchoring AS1411 on the surface of macrophages provided a novel approach to construct engineered macrophages for tumor immunotherapy.

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