What question did this study set out to answer?

To investigate the potential of EPIC, a novel polymer, in inducing pyroptosis for cancer immunotherapy.

April 5, 2026

Abstract 4313: Light-free photochemical internalization-inducing polymer conjugate elicits cancer pyroptosis to coordinate host immune responses

Key Points

To investigate the potential of EPIC, a novel polymer, in inducing pyroptosis for cancer immunotherapy.
Developed EPIC that activates in lysosomes when exposed to cathepsin B.
Assessed the generation of reactive oxygen species and lysosomal membrane destabilization in cancer cells.
Evaluated immune response effects in tumor-bearing mice following systemic administration of EPIC.
Combined EPIC with anti-PD-1 checkpoint blockade to study enhanced T cell infiltration.
EPIC induced strong oxidative stress leading to pyroptosis in cancer cells.
Triggered significant immune responses, including dendritic cell maturation and NK cell activation.
Combining EPIC with anti-PD-1 resulted in over 50% complete remission in treated mice.

Abstract

Abstract Gasdermin-D-mediated pyroptosis, an immunogenic cell death primarily occurring in antigen-presenting cells, plays a pivotal role in coordinating both innate and adaptive immune responses. Therefore, it holds immense potential for cancer immunotherapy. However, its spatiotemporal control within the tumor microenvironment remains challenging. We developed EPIC (Enzymatically switchable Pyroptosis-Inducing polymer Conjugate) within lysosomes upon exposure to cathepsin B, an enzyme overexpressed in many cancers. Upon in vitro exposure to cancer cells, EPIC generates reactive oxygen species via self-immolation-mediated CRET. The resulting oxidative stress induces lysosomal membrane destabilization, which initiate a downstream signaling cascade leading to proteolytic cleavage of gasdermin-D. The cleaved gasdermin-D assembles into pyroptotic pores in the cell membrane, enabling the efflux of damage-associated molecular patterns and pro-inflammatory cytokines. Systemic administration of EPIC in tumor-bearing mice invokes a potent immune response by dendritic cell maturation and reinvigoration of cytotoxic NK cells. Notably, combining EPIC with anti-PD-1 checkpoint blockade enhances the infiltration of tumor-specific cytotoxic T lymphocytes, resulting in sustained tumor regression and complete remission in over 50% of treated mice. These findings underscore the potential of EPIC as a multifunctional, precisely activatable nanotherapeutic for effective cancer immunotherapy. Citation Format: Torsha Ghosh, Jae Hyung Park, Sol Shin, Soyoung Son, . Light-free photochemical internalization-inducing polymer conjugate elicits cancer pyroptosis to coordinate host immune responses abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4313.

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Cite This Study

Ghosh et al. (Fri,) studied this question.

synapsesocial.com/papers/69d1fd62a79560c99a0a3557 https://doi.org/https://doi.org/10.1158/1538-7445.am2026-4313

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