Generation of personalized whole tumor cells vaccine for pyroptosis-enhanced anticancer immunity via Cu2-xSe photothermal activation under NIR irradiation

Autologous tumor cells demonstrate considerable promise as individualized therapeutic vaccines owing to their endogenous neoantigen repertoire. Nevertheless, their suboptimal immunogenicity substantially impedes clinical translation. Herein, we engineered an innovative whole tumor cell vaccine platform utilizing photothermal Cu_2-xSe nanoparticles, which encapsulate comprehensive tumor-associated antigens and intrinsic immunostimulatory molecules to elicit a polyvalent antitumor immune response. In this work, Cu_2-xSe was applied to prepare the whole tumor cell vaccine for the first time. As a pyroptosis inducer, Cu_2-xSe triggered the expression of damage-associated molecular patterns (DAMPs) as endogenous adjuvants in 4T1 cells (mouse breast cancer cells) under near-infrared (NIR) irradiation. Repeated freeze-thaw cycles inactivated and lysed Cu_2-xSe-loaded 4T1 cells, releasing DAMPs for laser-activated Cu_2-xSe-based whole tumor cell vaccine (LC-TCV) preparation. Mild photothermal therapy (PTT) at the vaccination site by NIR irradiation effectively suppressed tumor growth. This efficacy was primarily attributed to the synergistic effects of multiple natural antigens and adjuvants in LC-TCV, which promoted dendritic cells (DCs) maturation and subsequent immune activation. Consequently, it potentiates the recruitment of cytotoxic T lymphocytes, elicits immunogenic cell death (ICD), and consequently initiates a potent antigen-specific immune cascade. Collectively, this study presents an innovative approach to unleash the potential of personalized whole tumor cell vaccines in cancer therapy.