Method of increasing the ratio of effector T cells to regulatory T cells in a tumor by administering to a subject a TGF-beta inhibitor and a PD-1 antibody
AssigneesXoma Technology Ltd., The Regents of the University of California
InventorsAmer M. Mirza, Rosemary J. Akhurst, Ou Li
Life of this patent
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Abstract
The present disclosure relates, in general, to combination therapy using an inhibitor of transforming growth factor beta (TGFβ) and an inhibitor of programmed cell death protein 1 (PD-1) for treating cancer or preventing recurrence of cancer diseases such as lung cancer, prostate cancer, breast cancer, hepatocellular cancer, esophageal cancer, colorectal cancer, pancreatic cancer, bladder cancer, kidney cancer, ovarian cancer, stomach cancer, fibrotic cancer, glioma and melanoma, and metastases thereof.
Claims16
A method for increasing the ratio of effector T cells to regulatory T cells in a tumor comprising administering to a subject in need thereof therapeutically effective amounts of an inhibitor of transforming growth factor beta (TGFβ) and an antibody that binds Programmed cell death protein 1 (PD-1), wherein the TGFβ inhibitor is an antibody that binds transforming growth factor beta (TGFβ)1, TGFβ2 and TGFβ3 comprising:
- I.
- (a) a heavy chain CDR1 amino acid sequence set forth in SEQ ID NO:
- 19;
- (b) a heavy chain CDR2 amino acid sequence set forth in SEQ ID NO:
- 20;
- (c) a heavy chain CDR3 amino acid sequence set forth in SEQ ID NO:
- 21;
- (d) a light chain CDR1 amino acid sequence set forth in SEQ ID NO:
- 22;
- (e) a light chain CDR2 amino acid sequence set forth in SEQ ID NO:
- 23;
- and
- (f) a light chain CDR3 amino acid sequence set forth in SEQ ID NO:
- 24;
- or
- II.
- (a) a heavy chain CDR1 amino acid sequence set forth in SEQ ID NO:
- 25;
- (b) a heavy chain CDR2 amino acid sequence set forth in SEQ ID NO:
- 26;
- (c) a heavy chain CDR3 amino acid sequence set forth in SEQ ID NO:
- 27;
- (d) a light chain CDR1 amino acid sequence set forth in SEQ ID NO:
- 28;
- (e) a light chain CDR2 amino acid sequence set forth in SEQ ID NO:
- 29;
- and
- (f) a light chain CDR3 amino acid sequence set forth in SEQ ID NO:
- 30;
- or
- III.
- (a) a heavy chain CDR1 amino acid sequence set forth in SEQ ID NO:
- 25;
- (b) a heavy chain CDR2 amino acid sequence set forth in SEQ ID NO:
- 26;
- (c) a heavy chain CDR3 amino acid sequence set forth in SEQ ID NO:
- 27;
- (d) a light chain CDR1 amino acid sequence set forth in SEQ ID NO:
- 16;
- (e) a light chain CDR2 amino acid sequence set forth in SEQ ID NO:
- 17;
- and
- (f) a light chain CDR3 amino acid sequence set forth in SEQ ID NO:
- 18.
Dependencies are inferred from the claim text.