Tumor-associated macrophages (TAMs), a key subpopulation in the tumor microenvironment, are often associated with poor outcomes among cancer patients. Derived from circulating monocytes, TAMs are directly involved in solid tumor proliferation and angiogenesis, making them an ideal target for anti-cancer therapies. Monocyte-derived dendritic cells (moDCs), however, play a critical role in antigen cross-presentation, and have been shown to independently facilitate CD4+ and CD8+ T cell differentiation, enabling anti-tumor immune responses. This project aims to develop an mRNA vaccine that targets circulating monocytes to drive cellular differentiation towards moDCs. An mRNA-LNP platform is of interest.

Our approach is threefold: optimizing LNP stability via combinatorial ionizable lipid libraries; development and integration of antigen-encoding mRNA into the platform; synthesis and maleimide-based conjugation of monocyte-targeting ligands. Tumor growth and survival of mice bearing MC38, a variant of colorectal adenocarcinoma, will be monitored to evaluate the antitumor efficacy of monocyte targeted LNPs. By inducing monocyte differentiation into moDCs in-vivo, we seek to enhance the immune system’s ability to fight against hard-to-treat cancers.

Through the SuperUROP program, I’m hoping to continue my work in the mRNA vaccine space, while gaining more scientific independence. I’m also excited to solidify my research interests, especially as I begin to prepare for graduate school applications. During the span of the academic year, I’m also interested in finalizing a paper.