<u>Abstract</u>: The generation of immunogenic cell death (ICD) by drug, chemical and physical stimuli has the potential to induce anti-tumor immunity by cell death mechanisms that facilitate the presentation of tumor neo-antigens plus the release of danger-associated molecular patterns in a wide range of cancers.  Moreover, this endogenous vaccination approach can be combined with multiple immune adjuvants, checkpoint inhibitors and other treatment modalities to allow propagation of the ICD-induced immune in heterogeneous tumor microenvironments (TME).  In this presentation, Dr Nel will elucidate the use of different nanoparticle compositions for therapeutic intervention in pancreatic ductal adenocarcinoma (PDAC) and triple negative breast cancer (TNBC) through the delivery of chemotherapeutic agents that induce different ICD response pathways, requiring creative use of combination therapy (including by the same nanoparticle) to obtain treatment synergy.  This will include discussion of the use of a novel ICD pathway that is premised on interference in lysosome fusion and autophagy flux by the topoisomerase I inhibitory, irinotecan, for PDAC treatment in combination with checkpoint inhibitor therapy. Dr Nel will also discuss the use of chemotherapeutic agents that selectively activate cytotoxic T-cell versus NK-mediated tumor cell killing in the heterogeneous TNBC environment by nanocarriers delivering lipid-based prodrugs and inhibitors of T-cell exclusion pathways.  The talk will conclude with a discussion of the advantages and pitfalls of ICD intervention in the clinic.

Multi-functional nanocarrier platforms for anti-cancer immunity in heterogeneous tumor microenvironments

ACS Spring 2022

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