A self-assembled, genetically engineered, irradiated tumor cell debris vaccine

Yajie Sun; Yan Hu; Yuanyuan Geng; Chao Wan; Yang Liu; Yifei Liao; Xiujuan Shi; Jonathan F. Lovell; Kunyu Yang; Honglin Jin

doi:10.1002/EXP.20220170

Exploration ›› 2024, Vol. 4 ›› Issue (5) : 20220170 DOI: 10.1002/EXP.20220170

RESEARCH ARTICLE

A self-assembled, genetically engineered, irradiated tumor cell debris vaccine

Yajie Sun ¹^,²
, Yan Hu ¹^,²
, Yuanyuan Geng ³
, Chao Wan ¹^,²
, Yang Liu ⁴
, Yifei Liao ⁵
, Xiujuan Shi ³
, Jonathan F. Lovell ⁶
, Kunyu Yang ¹^,²^,^†
, Honglin Jin ¹^,³^,^†

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Abstract

Vaccine-based therapeutics for cancers face several challenges including lack of immunogenicity and tumor escape pathways for single antigen targets. It has been reported that radiotherapy has an in situ vaccine effect that provides tumor antigens following irradiation, helping to activate antigen-presenting cells (APCs). Herein, a new vaccine approach is developed by combining genetically engineered irradiated tumor cell debris (RTD) and hyaluronic acid (HA), termed HA@RTD. A cancer cell line is developed that overexpresses granulocyte-macrophage colony-stimulating factor (GMCSF). A hydrogel was developed by covalent conjugation of HA with RTD proteins that acted as a potent vaccine system, the effects which were probed with T cell receptor sequencing. The engineered vaccine activated antitumor immunity responses and prevented tumor growth in mice even with a single immunization. HA@RTD vaccine efficacy was also assessed in therapeutic settings with established tumors and in combination with immune checkpoint blockade.

Keywords

anti-PD-1 / cancer immunotherapy / cancer vaccine / genetically modified tumor membrane / hydrogel / lung cancer / radiated tumor cell debris

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Yajie Sun, Yan Hu, Yuanyuan Geng, Chao Wan, Yang Liu, Yifei Liao, Xiujuan Shi, Jonathan F. Lovell, Kunyu Yang, Honglin Jin. A self-assembled, genetically engineered, irradiated tumor cell debris vaccine. Exploration, 2024, 4(5): 20220170 DOI:10.1002/EXP.20220170

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