Compositions and Methods for Targeting Stromal Cells for the Treatment of Cancer
AssigneesThe Trustees of the University of Pennsylvania, The Wistar Institute of Anatomy and Biology
InventorsCarl H. June, Ellen Puré, Liang-Chuan Wang, Steven Albelda, John Scholler
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Abstract
The present invention provides compositions and methods for treating cancer in a human. The invention relates to targeting the stromal cell population in a tumor microenvironment. For example, in one embodiment, the invention provides a composition that is targeted to fibroblast activation protein (FAP). The invention includes a chimeric antigen receptor (CAR) which comprises an anti-FAP domain, a transmembrane domain, and a CD3zeta signaling domain.
Claims19
-8. (canceled)
A nucleic acid encoding a chimeric antigen receptor (CAR), wherein the CAR comprises an antigen binding domain derived from an F19 binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain, wherein the antigen binding domain binds to a stromal cell antigen, and wherein the antigen binding domain comprises:
- (a) a light chain variable region comprising a light chain complementary region 1 comprising the amino acids 24-39 of SEQ ID NO:9 (RSSQSIVHSNGNTYLE), a light chain complementary region 2 comprising the amino acids 55-61 of SEQ ID NO:
- 9 (KVSNRFS), a light chain complementary region 3 comprising amino acids 94-102 of SEQ ID NO:
- 9 (FGGSHVPYT);
- or
- (b) a heavy chain variable region comprising a heavy chain complementary region 1 comprising the amino acids 30-34 of SEQ ID NO:
- 8 (SYGMS), a heavy chain complementary region 2 comprising the amino acids 49-65 of SEQ ID NO:
- 8 (TTNNNGGVTYYPDSVKG), a heavy chain complementary region 3 comprising the amino acids 98-105 SEQ ID NO:
- 8 (YGYYAMDY).
A modified immune cell comprising a chimeric antigen receptor (CAR), wherein the CAR comprises an antigen binding domain derived from an F19 monoclonal antibody, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain, wherein the antigen binding domain binds to a stromal cell antigen, wherein the antigen binding domain binds to a stromal cell antigen, and wherein the antigen binding domain comprises:
- (a) a light chain variable region comprising a light chain complementary region 1 comprising the amino acids 24-39 of SEQ ID NO:9 (RSSQSIVHSNGNTYLE), a light chain complementary region 2 comprising the amino acids 55-61 of SEQ ID NO:
- 9 (KVSNRFS), a light chain complementary region 3 comprising amino acids 94-102 of SEQ ID NO:
- 9 (FGGSHVPYT);
- or
- (b) a heavy chain variable region comprising a heavy chain complementary region 1 comprising the amino acids 30-34 of SEQ ID NO:
- 8 (SYGMS), a heavy chain complementary region 2 comprising the amino acids 49-65 of SEQ ID NO:
- 8 (TTNNNGGVTYYPDSVKG), a heavy chain complementary region 3 comprising the amino acids 98-105 SEQ ID NO:
- 8 (YGYYAMDY).
A method of treating a tumor in a subject in need thereof, the method comprising administering to the subject an effective amount of a modified immune cell comprising a chimeric antigen receptor (CAR), wherein the CAR comprises an antigen binding domain derived from an F19 monoclonal antibody, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain, wherein the antigen binding domain binds to a stromal cell antigen, wherein the antigen binding domain binds to a stromal cell antigen, and wherein the antigen binding domain comprises:
- (a) a light chain variable region comprising a light chain complementary region 1 comprising the amino acids 24-39 of SEQ ID NO:9 (RSSQSIVHSNGNTYLE), a light chain complementary region 2 comprising the amino acids 55-61 of SEQ ID NO:
- 9 (KVSNRFS), a light chain complementary region 3 comprising amino acids 94-102 of SEQ ID NO:
- 9 (FGGSHVPYT);
- or
- (b) a heavy chain variable region comprising a heavy chain complementary region 1 comprising the amino acids 30-34 of SEQ ID NO:
- 8 (SYGMS), a heavy chain complementary region 2 comprising the amino acids 49-65 of SEQ ID NO:
- 8 (TTNNNGGVTYYPDSVKG), a heavy chain complementary region 3 comprising the amino acids 98-105 SEQ ID NO:
- 8 (YGYYAMDY).
Dependencies are inferred from the claim text.