COMPOSITIONS TO DISRUPT PROTEIN KINASE A ANCHORING AND USES THEREOF

摘要

The invention provides compositions and methods for treating diseases associated with expression of a cancer associated antigen as described herein. The invention also relates to chimeric antigen receptor (CAR) specific to a cancer associated antigen and modified T-cell receptor (TCR) T cells as described herein, vectors encoding the same, and recombinant T cells comprising the CARs or TCRs of the present invention. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises an antigen binding domain that binds to a cancer associated antigen as described herein. In one aspect, the invention includes a composition comprising a nucleic acid sequence encoding a T cell signaling molecule and a nucleic acid sequence encoding a peptide comprising an amphipathic helix domain and a cluster of basic amino acids, wherein the peptide disrupts protein kinase A and an A-kinase anchoring protein (AKAP) association. The invention also includes a peptide that disrupts the PKA and AKAP association, such as through binding the RI subunit of the PKA with high affinity, thus preventing PKA from anchoring to the cell membrane.