Exit Seminar: Abishek Wadhwa

Developing lipid nanoparticles to reprogram the tumour microenvironment for cancer immunotherapy: A high-resolution multi-omic approach

Cancer is a leading cause of death in Canada and worldwide. Targeting tumour-resident immune cells using mRNA-lipid nanoparticles (mRNA-LNPs) is a compelling approach for cancer immunotherapy. LNP composition can profoundly impact tissue tropism and cellular responses, yet most screening techniques focus exclusively on biodistribution and fall short in characterizing transcriptional profiles and functional protein expression. Therefore, I developed a high-throughput LNP screening platform: multi organ, multi-omic nanoparticle analysis by sequencing (MOMONA-seq) to characterize cellular responses of mRNA-LNPs at single-cell resolution. I harnessed MOMONA-seq to identify an mRNA-LNP formulation that preferentially targets tumour-associated macrophages (TAMs), induces oxidative stress and pro-inflammatory reprogramming of the tumour microenvironment, thus eliciting CD8+ T cell-dependent antitumour immunity. MOMONA-seq enables high-throughput, high-resolution LNP screening, and provides a powerful framework for rational LNP design in cancer immunotherapy.