Cell Discovery (Oct 2024)

Developing an erythrocyte‒MHC-I conjugate for cancer treatment

  • Yuehua Liu,
  • Xiaoqian Nie,
  • Xingyun Yao,
  • Huafeng Shou,
  • Yang Yuan,
  • Yun Ge,
  • Xiangmin Tong,
  • Hsiang-Ying Lee,
  • Xiaofei Gao

DOI
https://doi.org/10.1038/s41421-024-00713-9
Journal volume & issue
Vol. 10, no. 1
pp. 1 – 14

Abstract

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Abstract Mature erythrocytes are known to lack major histocompatibility complex (MHC) proteins. However, the presence of MHC molecules on erythrocytes has been occasionally reported, though without a defined function. In this study, we designed erythrocyte conjugated solely with a fusion protein consisting of an antigenic peptide linked to MHC class I (MHC-I) protein, termed MHC-I‒Ery. The modified erythrocyte, decorated with the peptide derived from human papillomavirus (HPV) 16 oncoprotein E6/E7, effectively activated antigen-specific CD8+ T cells in peripheral blood mononuclear cells (PBMCs) from HPV16+ cervical cancer patients. Additionally, MHC-I‒Ery monotherapy was shown to inhibit antigen-positive tumor growth in mice. This treatment immediately activated CD8+ T cells and reduced suppressive myeloid cells in the spleen, leading to systemic anti-tumor activity. Safety and tolerability evaluations of MHC-I‒Ery in non-human primates further supported its clinical potential. Our results first demonstrated that erythrocytes equipped solely with antigen peptide‒MHC-I complexes can robustly stimulate the immune system, suggesting a novel and promising approach for advancing cancer immunotherapy.