A modular protein approach to next-generation in situ cancer vaccines: A commentary

Abstract

Cancer immunotherapy has revolutionized in situ vaccination approaches that leverage endogenous tumor antigens to initiate immune responses. This commentary examines the protease-activated PSTAGylated in situ tumor vaccine (PPTV), a modular metalloprotein platform engineered for precise co-delivery of mitochondria-disrupting peptides and manganese ions. Utilizing ferritin as a biodegradable chassis, PPTV achieves tumor-specific activation through matrix metalloproteinase 14 cleavage, inducing immunogenic cell death and activating the stimulator of interferon genes pathway. Preclinical models demonstrate potent antitumor immunity, with combination therapy eradicating established tumors. The integration of patient-derived organoids is proposed to personalize immunotherapy, highlighting the translational potential of biomaterial-based vaccines for overcoming present limitations in cancer treatment.

Keywords

Cancer immunotherapy / Metalloprotein / Immunogenic cell death / Stimulator of interferon genes pathway / Patient-derived organoids

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