METHODS AND COMPOSITIONS FOR THE TREATMENT OF CANCER
Provided herein are methods for adoptive cell transfer for the treatment of cancer, comprising administering a therapeutically effective amount of immune cells having antitumor activity to a subject, wherein the immune cells are contacted with a protein transduction domain (PTD)-MYC fusion polypeptide prior to administration to the subject. In some embodiments, the PTD-MYC fusion polypeptide comprises: (i) an HIV TAT protein transduction domain; and (ii) a MYC polypeptide sequence.
1 . A composition comprising:
(a) a MYC fusion peptide, comprising (i) a protein transduction domain; (ii) a MYC polypeptide sequence; and
(b) one or more primary immune cells isolated from a donor subject that has a solid tumor, wherein the one or more primary immune cells are reactive against a tumor-specific antigen.
2 . The composition of claim 1 , wherein the solid tumor is a carcinoma, adenoma, adenocarcinoma, blastoma, sarcoma, or lymphoma.
3 . The composition of claim 1 , wherein the solid tumor is a metastatic tumor.
4 . The composition of claim 1 , wherein the solid tumor is a basal cell carcinoma, biliary tract cancer, bladder cancer, breast cancer, cervical cancer, choriocarcinoma, CNS cancer, colon cancer, colorectal cancer, connective tissue cancer, cancer of the digestive system, endometrial cancer, esophageal cancer, eye cancer, gastric cancer, glial cell tumor, head and neck cancer, hepatoma, hepatic carcinoma, Hodgkin's lymphoma, Non-Hodgkin's lymphoma, intra-epithelial neoplasm, kidney cancer, larynx cancer, liver cancer, small-cell lung cancer, non-small cell lung cancer, melanoma, myeloma, neuroblastoma, oral cavity cancer, ovarian cancer, pancreatic cancer, prostate cancer, rectal cancer, renal cancer, cancer of the respiratory system, retinoblastoma, rhabdomyosarcoma, salivary gland carcinoma, squamous cell cancer, stomach cancer, testicular cancer, thyroid cancer, uterine cancer, cancer of the urinary system, or a vulvar cancer.
5 . The composition of any one of claims 1 - 4 , wherein the MYC fusion peptide comprises SEQ ID NO: 1.
6 . The composition of any one of claims 1 - 5 , wherein the one or more immune cells have antitumor activity against the solid tumor cells.
7 . The composition of any one of claims 1 - 6 , wherein the one or more immune cells comprises one or more lymphocytes.
8 . The composition of claim 7 , wherein the one or more lymphocytes comprises a T cell, a B cell, an NK cell, or any combination thereof.
9 . The composition of any one of claims 7 - 8 , wherein the one or more lymphocytes is a tumor-infiltrating lymphocyte, T-cell receptor modified lymphocyte, or a chimeric antigen receptor modified lymphocyte.
10 . The composition of claim 9 , wherein the tumor-infiltrating lymphocyte has a CD8+CD25+ signature or a CD4+CD25+ signature.
11 . The composition of any one of claims 1 - 10 , wherein the one or more immune cells comprises a detectable moiety.
12 . A method for treating a cancer in a subject, comprising administering one or more modified immune cells to the subject in need thereof, wherein the one or more modified immune cells comprise a MYC fusion peptide comprising (i) a protein transduction domain; (ii) a MYC polypeptide sequence and are reactive to a tumor-specific antigen.
13 . The method of claim 12 , wherein the one or more modified immune cells are derived from primary immune cells isolated from the subject.
14 . The method of claim 12 , wherein the one or more modified immune cells are derived from primary immune cells isolated from a separate donor subject having the same type of cancer.
15 . The method of any one of claims 12 - 14 , wherein the cancer is carcinoma or a sarcoma.
16 . The method of any one of claims 12 - 14 , wherein the cancer is metastatic cancer.
17 . The composition any one of claims 12 - 14 , wherein the cancer is a basal cell carcinoma, biliary tract cancer, bladder cancer, breast cancer, cervical cancer, choriocarcinoma, CNS cancer, colon cancer, colorectal cancer, connective tissue cancer, cancer of the digestive system, endometrial cancer, esophageal cancer, eye cancer, gastric cancer, glial cell tumor, head and neck cancer, hepatoma, hepatic carcinoma, Hodgkin's lymphoma, Non-Hodgkin's lymphoma, intra-epithelial neoplasm, kidney cancer, larynx cancer, liver cancer, small-cell lung cancer, non-small cell lung cancer, melanoma, myeloma, neuroblastoma, oral cavity cancer, ovarian cancer, pancreatic cancer, prostate cancer, rectal cancer, renal cancer, cancer of the respiratory system, retinoblastoma, rhabdomyosarcoma, salivary gland carcinoma, squamous cell cancer, stomach cancer, testicular cancer, thyroid cancer, uterine cancer, cancer of the urinary system, or a vulvar cancer.
18 . The method of any one of claims 13 - 17 , wherein the one or more modified immune cells are prepared by contacting the primary immune cells in vitro with the MYC fusion peptide following isolation.
19 . The method of any one of claims 13 - 17 , further comprising expanding the primary immune cells in vitro prior to prior to or following contacting with the MYC fusion peptide.
20 . The method of any one of claims 12 - 19 , wherein the MYC fusion peptide comprises SEQ ID NO: 1.
21 . The method of any one of claims 12 - 20 , wherein the one or more modified immune cells have antitumor activity against cancer cells in the subject.
22 . The method of any one of claims 12 - 21 , wherein the one or more modified immune cells comprise one or more anergic immune cells.
23 . The method of any one of claims 12 - 22 , wherein the one or more immune cells comprises one or more lymphocytes.
24 . The method of claim 23 , wherein the one or more lymphocytes comprises a T cell, a B cell, an NK, or any combination thereof.
25 . The method of claim 23 , wherein the one or more lymphocytes is a tumor-infiltrating lymphocyte, T-cell receptor modified lymphocyte, or a chimeric antigen receptor modified lymphocyte.
26 . The method of claim 25 , wherein the lymphocyte has a CD8 + CD28 − CD152 − signature, a CD8+CD25+ signature, or a CD4+CD25+ signature.
27 . The method of any one of claims 13 - 26 , wherein method further comprises isolating the primary immune cells from the donor subject.
28 . The method of any one of claims 12 - 27 , wherein the one or more modified immune cells are administered intravenously, intraperitoneally, subcutaneously, intramuscularly, or intratumorally.
29 . The method of any one of claims 12 - 28 , further comprising lymphodepleting the subject prior to administration of the one or more modified immune cells.
30 . The method of any one of claims 12 - 29 , further comprising administering a cytokine to the subject.
31 . The method of any one of claims 12 - 30 , wherein the subject is a human or an animal.
32 . The method of any one of claims 12 - 31 , further comprising administering an additional cancer therapy.
33 . A method for preparing modified immune cells for cancer therapy, comprising contacting one or more immune cells in vitro with a MYC fusion polypeptide, wherein the immune cells are from a donor that has been exposed to one or more tumor antigens and wherein the MYC fusion peptide comprises (i) a protein transduction domain; (ii) a MYC polypeptide sequence and are reactive to a tumor-specific antigen.
34 . The method of claim 33 , wherein the one or more modified immune cells are derived from primary immune cells isolated from a subject having cancer.
35 . The method of any one of claims 33 - 34 , further comprising expanding the primary immune cells in vitro prior to or following contacting with the MYC fusion peptide.
36 . The method of any one of claims 33 - 35 , wherein the MYC fusion peptide comprises SEQ ID NO: 1.
37 . The method of any one of claims 33 - 34 , wherein the one or more modified immune cells have antitumor activity.
38 . The method of any one of claims 33 - 37 , wherein the one or more immune cells comprises a T cell, a B cell, an NK, or any combination thereof.
39 . The method of any one of claims 33 - 37 , wherein the one or more immune cells is a tumor-infiltrating lymphocyte, T-cell receptor modified lymphocyte, or a chimeric antigen receptor modified lymphocyte.
40 . A method for increasing the efficacy of adoptive cell therapy or T-cell therapy in a subject comprising administering the composition of any of claims 1 - 11 .
41 . The composition of any of claims 1 - 11 for use in treating a cancer.
42 . Use of a composition of any one of claims 1 - 11 in the manufacture of a medicament for the treatment of a cancer.