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

Zhiren Wang, Wenpan Li, Jonghan Park, Karina Marie Gonzalez, Aaron James Scott, Jianqin Lu

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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-γ)-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.

Original languageEnglish (US)
Pages (from-to)929-939
Number of pages11
JournalJournal of Controlled Release
Volume349
DOIs
StatePublished - Sep 2022

Keywords

  • Camptothecin
  • Camptothesome
  • Clathrin-mediated endocytosis
  • Immune checkpoint blockade
  • Immunogenic cell death
  • Metastatic colorectal cancer

ASJC Scopus subject areas

  • Pharmaceutical Science

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