Compositions and methods for treating cancer with anti-BCMA immunotherapy
Chimeric antigen receptors containing BCMA antigen binding domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.
1. A method of treating a BCMA-expressing multiple myeloma in a human subject in need thereof, the method comprising administering to the human subject a pharmaceutical composition comprising an anti-tumor effective amount of a population of T cells, wherein each cell of the population of T cells comprises a nucleic acid sequence that encodes a chimeric antigen receptor (CAR), wherein the CAR comprises at least one extracellular antigen binding domain comprising a BCMA antigen binding domain comprising the amino acid sequence of SEQ ID NO: 78, at least one linker or at least one spacer domain, at least one transmembrane domain, at least one intracellular signaling domain, wherein the nucleic acid comprises a promoter operably linked to the CAR encoding sequence, and thereby treating the BCMA-expressing multiple myeloma of the human subject.
2. The method of claim 1 , wherein the at least one transmembrane domain comprises a transmembrane domain of a protein selected from the group consisting of: a T-cell receptor (TCR) alpha chain, a TCR beta chain, a TCR zeta chain, a CD8, a CD28, a CD3 epsilon, a CD45, a CD4, a CD5, a CD8, a CD9, a CD16, a CD22, a CD33, a CD37, a CD64, a CD80, a CD86, a CD134, a CD137 and a CD154.
3. The method of claim 1 , wherein the at least one extracellular antigen binding domain comprising the BCMA antigen binding domain, the at least one intracellular signaling domain, or both are connected to the at least one transmembrane domain by the at least one linker or the at least one spacer domain.
4. The method of claim 1 , wherein the at least one linker or the at least one spacer domain is obtained from the extracellular domain of CD8, TNFRSF19, or CD28, and is linked to the at least one transmembrane domain.
5. The method of claim 1 , wherein the at least one extracellular antigen binding domain comprising the BCMA antigen binding domain is preceded by a leader nucleotide sequence encoding a leader peptide.
6. The method of claim 1 , wherein the at least one intracellular signaling domain further comprises a CD3 zeta intracellular domain.
7. The method of claim 1 , wherein the nucleic acid sequence encoding the BCMA antigen binding domain comprises a nucleic sequence comprising SEQ ID NO: 77 or 105, or a sequence with 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity thereof.
8. The method of claim 1 , wherein the at least one intracellular signaling domain comprises a costimulatory domain, a primary signaling domain, or any combination thereof.
9. The method of claim 8 , wherein the costimulatory domain comprises a functional signaling domain selected from the group consisting of OX40, CD70, CD27, CD28, CD5, ICAM-1, LFA-1 (CD11a/CD18), ICOS (CD278), DAP10, DAP12, and 4-1BB (CD137).