Poster Session - Abstract # 25

Labeling Tumor Cells with Synthetic Constructs for Immune Detection

Matthew C. Russolillo, and Mark P. Farrell

Department of Medicinal Chemistry, University of Kansas, Lawrence, KS, USA

Immunotherapy is revolutionizing cancer therapy, but these therapies have yet to be broadly applied.  Immunotherapies used to treat refractory and relapsed hematologic malignances highlight the promise of immuno-oncology; however, the treatment of solid tumors with immunotherapies remains challenging.  One significant challenge impeding the treatment of solid tumors with immunotherapies is tumor antigen heterogeneity.  Solid tumors differentially express a wide range of antigens, yet antigen expression levels across a tumor are highly variable.  Unfortunately, variable antigen expression facilitates escape mechanisms and obstructs long-term remission.  Approaches to overcome the challenge of antigen heterogeneity have seen limited success; however, a recent combination therapy leveraging tumor targeting virions and chimeric antigen receptor (CAR) T cells has provided a glimmer of hope.  Here tumor targeting virions infect tumor cells and induce the expression of an antigen that permits tumor cell recognition and lysis by CAR-T cells.  Our approach is analogous to this combination therapy, but instead of using virions to induce antigen expression, we use synthetic molecules that deposit on the surface of tumor cells upon activation with tumor-specific or tumor-targeted enzyme.  These molecules carry antigens that facilitate tumor cell recognition and lysis by CAR-NK cells that we have developed.  Here we will describe our synthetic approach to these molecules and their initial biological characterization.