Compositions comprising chimeric antigen receptors, T cells comprising the same, and methods of using the same

A chimeric antigen receptor (CAR) molecule comprising a binding domain (BD), a transmembrane domain (TD), an intracellular signaling domain (ISD), and at least one costimulatory domain (CD), wherein:

• (i) the BD comprises a heavy chain complementary determining region 1 (HC CDR1) comprising SEQ ID NO:
• 8, a heavy chain complementary determining region 2 (HC CDR2) comprising SEQ ID NO:
• 9, and a heavy chain complementary determining region 3 (HC CDR3) comprising SEQ ID NO:
• 10;
• a light chain complementary determining region 1 (LC CDR1) comprising SEQ ID NO:
• 11, a light chain complementary determining region 2 (LC CDR2) comprising SEQ ID NO:
• 12, and a light chain complementary determining region 3 (LC CDR3) comprising SEQ ID NO:
• 13;
• and/or a heavy chain variable region comprising an amino acid sequence at least 95% identical to SEQ ID NO:
• 5 and a light chain variable region comprising an amino acid sequence at least 95% identical to SEQ ID NO:
• 7, provided that the heavy chain variable region comprises an HC CDR1 comprising SEQ ID NO:
• 8, an HC CDR2 comprising SEQ ID NO:
• 9, and an HC CDR3 comprising SEQ ID NO:
• 10, and the light chain variable region comprises an LC CDR1 comprising SEQ ID NO:
• 11, an LC CDR2 comprising SEQ ID NO:
• 12, and an LC CDR3 comprising SEQ ID NO:
• 13;
• and further wherein BD binds to a tumor-exclusive epitope of a human MUC1 polypeptide (tMUC);
• (ii) the TD comprises a transmembrane domain of a protein selected from the group consisting of the T-cell receptor (TCR) alpha chain, the TCR beta chain, the TCR zeta chain, CD28, CD3 epsilon, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137, and CD154;
• (iii) the ISD comprises a functional signaling domain of a 4-1BB polypeptide, a functional signaling domain of a CD3 zeta polypeptide, or both;
• and
• (iv) the CD comprises a functional signaling domain of a protein selected from the group consisting of OX40, CD2, CD3, CD27, CD28, CD5, ICAM-1, LFA-1 (CD11a/CD18), and 4-1BB (CD137), or any combination thereof.