Novel Peptide Based Therapeutic Approach of CAR- redirecting T Cells

Abstract

The major challenge in the implications of CAR-T therapy in solid tumors has been the development of tumor plasticity, both at cellular level and molecular level. The increasing tendency to design personalized therapeutic approaches, along with the known heterogeneity of solid tumors, puts forward the need to find new targets. Nucleolin, which overexpressed by variety of different cancer cells, but not on their normal counterparts, has been validated as a novel target for anticancer treatments. Additionally, its overexpression has been associated with cell differentiation, adhesion proliferation, mitogenesis and angiogenesis. Here, we generated a novel peptide based chimeric antigen receptor by linking a peptide-targeting the nucleolin (NCL) to the CD8 transmembrane domain followed by 4-1BB and CD3ζ intracellular domains, that via targeting NCL reduced MDA-MB-231 cell viability and proliferation while inducing apoptosis and increase intracellular cytokine secretion through T-cell activation. This strategy could extend the therapeutic opportunities for Breast cancers and, in particularly for Triple-negative Breast Cancer patients.