2024 Asia Conference on Lung Cancer (ACLC) - Poster & ePosters-PP01.25

PP01.25 - Jemma Arakelyan

Pdf Summary

This study explores the potential of gold(I) diamine complexes as a novel therapeutic strategy for treating malignant pleural mesothelioma (MPM), a highly aggressive cancer associated with asbestos exposure. MPM presents significant challenges due to its status as an "immunologically cold" tumor, characterized by low immune cell activity and infiltration, which limits treatment effectiveness. The research emphasizes the need for innovative therapies that can overcome these barriers.<br /><br />The study evaluates synthesized gold(I) diamine complexes for their cytotoxic effects on MPM cells both in vitro and in vivo. These complexes demonstrated promising cytotoxicity and were able to induce immunogenic cell death (ICD), a process marked by the release of damage-associated molecular patterns (DAMPs) like calreticulin, ATP, and HMGB1. The induction of ICD suggests these gold complexes could potentially engage and activate the immune system against MPM cells, offering a dual mechanism of action that combines direct cytotoxic effects with immune system activation.<br /><br />Preclinical evaluation included tests on AB1 murine mesothelioma cells and human mesothelioma cell lines, showing that treatment with gold(I) diamine complexes led to increased phagocytosis - a process where cancer cells are engulfed and destroyed by immune cells, thereby enhancing an immune response. Additionally, in vivo studies using a murine mesothelioma model revealed effective reduction in tumor volume and enhanced tumor control.<br /><br />The study's results suggest that gold(I) diamine complexes hold potential as effective treatments for MPM, but further investigation is required to fully elucidate their capacity as immunomodulating agents. These findings could pave the way for novel treatments that address current limitations in managing MPM by engaging the immune system in conjunction with direct cancer cell cytotoxicity.

Keywords

gold(I) diamine complexes

malignant pleural mesothelioma

asbestos exposure

immunologically cold tumor

immunogenic cell death

damage-associated molecular patterns

cytotoxic effects

immune system activation

preclinical evaluation

novel therapeutic strategy