Prostate-specific membrane antigen cars and methods of use thereof
AssigneeThe Trustees of the University of Pennsylvania
InventorsYangbing Zhao, Szu Hua Sharon Lin, Xiaojun Liu, Anne Chew
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Abstract
The present disclosure provides modified immune cells (e.g., modified T cells) comprising a chimeric antigen receptor (CAR) having affinity for a prostate-specific membrane antigen (PSMA) (e.g., human PSMA). The present disclosure provides modified immune cells (e.g., modified T cells) comprising a CAR having affinity for PSMA and a dominant negative receptor and/or a switch receptor. The present disclosure provides modified immune cells (e.g., modified T cells) comprising a CAR having affinity for PSMA and a dominant negative receptor and/or a switch receptor, wherein the modified cell is capable of expressing and secreting a bispecific antibody.
Claims20
A method of treating a cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a composition comprising a modified immune cell comprising:
- (a) a chimeric antigen receptor (CAR) having affinity for a prostate specific membrane antigen (PSMA) on a target cell, wherein the CAR comprises the amino acid sequence set forth in SEQ ID NO:105;
- and
- (b) a dominant negative receptor consisting of the amino acid sequence set forth in SEQ ID NO:115.
A method of treating a cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a composition comprising a modified immune cell comprising:
- (a) a chimeric antigen receptor (CAR) having affinity for a prostate specific membrane antigen (PSMA) on a target cell, wherein the CAR comprises the amino acid sequence set forth in SEQ ID NO:105;
- and
- (b) a truncated dominant negative variant of TGF-β receptor type II comprising the amino acid sequence set forth in SEQ ID NO:115.
A method of treating a cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a composition comprising a modified immune cell comprising:
- (a) a chimeric antigen receptor (CAR) having affinity for a prostate specific membrane antigen (PSMA) on a target cell, wherein the CAR comprises an antigen binding domain, a transmembrane domain, and an intracellular domain, and wherein the antigen binding domain comprises:
- (i) a heavy chain variable region (VH) that comprises the consensus sequence of SEQ ID NO:183, and/or
- (ii) a light chain variable region (VL) that comprises the consensus sequence of SEQ ID NO:184;
- and
- (b) a dominant negative receptor and/or switch receptor.
Dependencies are inferred from the claim text.