COMPOSITIONS AND METHODS OF SYNTHETIC CTLA-4 TAILS FOR REPROGRAMMING OF CAR-T CELLS AND ENHANCEMENT OF ANTI-TUMOR EFFICACY

Abstract: compositions and methods for improved act are provided. compositions of car-t cells including car modified by fusion with one or more copies of a polypeptide including from 20 to 44 amino acids from the transmembrane and/or cytosolic domain of ctla-4 (ct) are described. car-ct-t cells have reduced trogocytosis, reduced t-cell fratricide, enhanced tumor antigen presentation and overall enhanced anti-tumor efficacy as compared with car-t cells lacking the ct domain(s). in preferred embodiments, car-tc fusion peptides include a ct domain having 2 copies of the yvkm motif. the compositions and methods provide enhanced car-t cell therapy for cancer, auto-immune disease as well as other disease and disorders. also disclosed are genetically modified cells and pharmaceutical compositions and methods of use thereof for treating subjects having diseases or disorders.

Inventor(s): Sidi Chen, Xiaoyu Zhou

CPC Classification: A61K35/17 (PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms ; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles ; soap compositions ))

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