Methods and compositions for cells expressing a chimeric intracellular signaling molecule
AssigneesThe Trustees of the University of Pennsylvania, Wayne State University
InventorsCarl H. June, Michael Milone, Yangbing Zhao, Lawrence G. Lum, Archana Thakur
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Abstract
The present invention relates to compositions and methods for enhancing T cell metabolism and activity for more effective adoptive T cell therapy. By expressing an chimeric antigen receptor and bispecific antibodies in T cells, the T cells are metabolically enhanced with improved cytotoxicity and resistance to immunosuppression imposed by tumor microenvironments. Certain aspects include modified T cells and pharmaceutical compositions comprising the modified cells for adoptive cell therapy and treating a disease or condition associated with enhanced immunity.
Claims8
A method of metabolically enhancing a tumor specific T cell, comprising:
- introducing a first nucleic acid encoding a chimeric antigen receptor (CAR) into a T cell in vitro to obtain a CAR T cell, wherein the CAR comprises an antigen binding domain that binds to CD19, a transmembrane domain, and intracellular signaling domains of a 4-1BB molecule and a CD3zeta molecule;
- arming the CAR T cell in vitro with a bispecific antibody, wherein arming the CAR T cell comprises introducing a second nucleic acid encoding the bispecific antibody into the CAR T cell, wherein the bispecific antibody binds CD3 on the CAR T cell, and wherein the bispecific antibody is capable of binding to an antigen on a tumor cell in vivo;
- and
- administering the armed CAR T cell to a CD19+ subject wherein the intracellular signaling domain is activated, thereby metabolically enhancing the tumor specific T cell.
Dependencies are inferred from the claim text.