Prostate-specific membrane antigen cars and methods of use thereof

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, wherein the modified immune cell comprises:

• (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:
• (i) the antigen binding domain comprises a heavy chain variable region and a light chain variable region selected from the group consisting of:
• (a) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:
• 21 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:
• 16;
• (b) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:
• 28 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:
• 33;
• (c) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:
• 40 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:
• 45;
• (d) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:
• 52 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:
• 57;
• (e) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:
• 64 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:
• 69;
• or
• (f) a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO:
• 191 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO:
• 192;
• and
• (ii) the intracellular domain comprises a 4-1BB signaling domain, an ICOS signaling domain, and a CD3 zeta signaling domain;
• and
• (b) a dominant negative 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, wherein the modified immune cell comprises:

• (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 an antibody or an antigen-binding fragment thereof comprising:
• (i) a heavy chain variable region (VH) that comprises the consensus sequence of SEQ ID NO:194, and/or
• (ii) a light chain variable region (VL) that comprises the consensus sequence of SEQ ID NO:
• 195;
• and
• (b) a dominant negative receptor and/or switch receptor.