Camptothesome elicits immunogenic cell death to boost colorectal cancer immune checkpoint blockade

Camptothesome is an innovative nanovesicle therapeutic comprising the sphingomyelin-derived camptothecin (CPT) lipid bilayer. In this work, we deciphered that Camptothesome was taken up by colorectal cancer (CRC) cells through primarily the clathrin-mediated endocytotic pathway and displayed the potential of eliciting robust immunogenic cancer cell death (ICD) via upregulating calreticulin, high mobility group box 1 protein (HMGB-1), and adenosine triphosphate (ATP), three hallmarks involved in the induction of ICD. In addition, use of dying MC38 tumor cells treated with Camptothesome as vaccine prevented tumor growth in 60% mice that received subsequent injection of live MC38 cells on the contralateral flank, validating Camptothesome was a legitimate ICD inducer in vivo. Camptothesome markedly reduced the acute bone marrow toxicity and gastrointestinal mucositis associated with free CPT and beat free CPT and Onivyde on anti-CRC efficacy and immune responses in a partially interferon gamma (IFN-gamma)-dependent manner. Furthermore, Camptothesome enhanced the efficacy of immune checkpoint inhibitors to shrink late-stage orthotopic MC38 CRC tumors with diminished tumor metastasis and markedly prolonged mice survival.

Automated summary

Camptothesome is an innovative nanovesicle therapeutic that has shown promising results in the treatment of colorectal cancer. It is taken up by cancer cells through a specific pathway and induces immunogenic cancer cell death. The use of Camptothesome-treated tumor cells as a vaccine has proven effective in preventing tumor growth. Furthermore, Camptothesome demonstrates superior anti-cancer efficacy and immune response compared to other treatments. It also enhances the effectiveness of immune checkpoint inhibitors in shrinking late-stage CRC tumors and prolonging survival.