Work

Enhancing anti-tumor immunity through intratumoral combination therapy with amphiphilic conjugates of oxaliplatin and imidazoquinoline TLR7/8 agonist

Year: 2025

Type: article

Abstract: , IMDQ), and an alkyl lipid. We hypothesized that such a lipidated conjugate would, upon intratumoral injection, increase the residence time in the tumor and reduce systemic dissemination and, hence, off-target toxicity. Whereas combination therapy with OxPt and IMDQ in native form improved, relative to single treatment, the anti-tumor efficacy against the primary treated tumor and a secondary distal tumor, this was not the case for OxPt-IMDQ-lipid conjugate therapy. We then altered the molecular design of the combination therapy and synthesized amphiphilic OxPt and IMDQ conjugates, comprising a cholesteryl motif and a hydrophilic poly(ethylene glycol) (PEG) chain. Intratumoral combination therapy with OxPt-PEG-cholesteryl and IMDQ-PEG-cholesteryl reduced, compared to native drug compounds, systemic innate inflammatory responses, and more efficiently eradicated primary and distal tumors. Furthermore, we found that combination therapy with OxPt-PEG-cholesteryl and IMDQ-PEG-cholesteryl induced antigen-specific anti-tumor responses and high infiltration levels of CD8+ T cells into the tumor.

Source: RSC Advances

DOI: 10.1039/d5ra00163c