JPWO2021146213A5

JPWO2021146213A5 -

Info

Publication number: JPWO2021146213A5
Application number: JP2022542739A
Authority: JP
Publication date: 2024-01-18

Claims

An expression vector for use in a method of treating cancer comprising administering an expression vector to an individual in need thereof, wherein the expression vector comprises:
a. a first insert comprising a nucleic acid sequence encoding a granulocyte macrophage colony stimulating factor (GM-CSF) sequence; and
b. a second insert comprising the sequence set forth in SEQ ID NO: 4 ;
including ;
An expression vector in which the individual is negative for homologous recombination deficiency (HRD) and/or the individual has a wild-type BRCA1 gene, a wild-type BRCA2 gene, or a combination thereof .

The cancers selected include solid tumor cancer, ovarian cancer, adrenocortical cancer, bladder cancer, breast cancer, cervical cancer, bile duct cancer, colorectal cancer, esophageal cancer, glioblastoma, and glioblastoma. tumor, hepatocellular carcinoma, head and neck cancer, kidney cancer, leukemia, lymphoma, lung cancer, melanoma, mesothelioma, multiple myeloma, pancreatic cancer, pheochromocytoma, plasmacytoma, neuroblastoma, 2. An expression vector for use according to claim 1 from the group consisting of prostate cancer, sarcoma, gastric cancer, uterine cancer, thyroid cancer, and hematological cancer,
Optionally said cancer is ovarian cancer, breast cancer, melanoma, or lung cancer; and
Optionally, the selection of solid tumor cancer is endometrial cancer, bile duct cancer, bladder cancer, hepatocellular carcinoma, gastric/esophageal cancer, ovarian cancer, melanoma, breast cancer, pancreatic cancer, Colorectal cancer, glioma, non-small cell lung cancer, prostate cancer, cervical cancer, kidney cancer, thyroid cancer, neuroendocrine cancer, small cell lung cancer, sarcoma, head and neck cancer, brain cancer , clear cell renal cell carcinoma, skin cancer, endocrine tumor, thyroid cancer, tumor of unknown primary origin, and gastrointestinal stromal tumor.

ovarian cancer has been substantially eradicated in said individual, and said method prevents or delays re-aggression of said substantially eradicated ovarian cancer, optionally wherein said substantially eradicated ovarian cancer 3. An expression vector for use according to claim 2, wherein the cancer is stage III or stage IV ovarian cancer.

The expression vector according to any one of claims 1 to 3, wherein the expression vector is administered into autologous cancer cells.

An autologous tumor cell transfected with an expression vector for use in a method of treating ovarian cancer having a wild-type BRCA1 gene, a wild-type BRCA2 gene, or a combination thereof, the method comprising: , administering said autologous tumor cells to an individual in need thereof, wherein said expression vector comprises:
a. a first insert comprising a nucleic acid sequence encoding a granulocyte macrophage colony stimulating factor (GM-CSF) sequence; and
b. A second insert containing the sequence set forth in SEQ ID NO: 4
administering to said individual autologous tumor cells transfected with an expression vector comprising.

Autologous tumor cells transfected with an expression vector for use according to claim 5, wherein said method comprises administering to an individual one or more doses of an autologous tumor cell vaccine comprising said autologous tumor cells. .

Autologous tumor cells transfected with an expression vector for use according to claim 5 or 6, wherein said autologous tumor cells are an autologous tumor cell vaccine.

An expression vector for use in a method of preventing or delaying recurrence of ovarian cancer in an individual in need thereof, the method comprising:
i. a first insert comprising a nucleic acid sequence encoding a granulocyte macrophage colony stimulating factor (GM-CSF) sequence; and
b. A second insert containing the sequence set forth in SEQ ID NO: 4
administering to said individual an expression vector comprising
the individual is homologous recombination repair defect (HRD) negative and/or
An expression vector in which the individual has a wild-type BRCA1 gene, a wild-type BRCA2 gene, or a combination thereof.

An expression vector for use according to any one of claims 5 to 8, wherein the individual is homologous recombination repair defect (HRD) negative and has a wild type BRCA2 gene; or
the individual is homologous recombination repair defect (HRD) negative and has a wild-type BRCA1 gene; or
An expression vector in which the individual is negative for homologous recombination repair defect (HRD) and has a combination of a wild-type BRCA1 gene and a wild-type BRCA2 gene.

Expression for use according to any one of claims 5 to 9, wherein the ovarian cancer is stage III or stage IV ovarian cancer and/or the ovarian cancer is refractory ovarian cancer. A vector,
Optionally, said refractory ovarian cancer is refractory to chemotherapy;
further optionally said chemotherapy comprises a platinum drug or a taxane, and
Further optionally, the platinum formulation comprises carboplatin and the taxane comprises paclitaxel.

An expression vector for use according to any one of claims 5 to 10, further comprising administering an additional therapeutic agent,
Optionally said additional therapeutic agent is selected from the group consisting of an angiogenesis inhibitor, a PARP inhibitor, and a checkpoint inhibitor for said individual;
Further optionally, the angiogenesis inhibitor is a vascular endothelial growth factor (VEGF) inhibitor, and the checkpoint inhibitor is a PD-1 inhibitor, a PD-L1 inhibitor, a CTLA-4 inhibitor, pembrolizumab, selected from the group consisting of nivolumab, cemiplimab, atezolizumab, avelumab, durvalumab, and ipilimumab;
Further optionally, said VEGF inhibitor is selected from the group consisting of sorafenib, sunitinib, bevacizumab, pazopanib, axitinib, cabozantinib, and revatinib, and
Further optionally, the VEGF inhibitor is bevacizumab, and the PARP inhibitor is selected from the group consisting of niraparib, olaparib, rucaparib, niraparib, talazoparib, veliparib, and pamiparib.

Expression vector for use according to any one of claims 1 to 11, wherein said GM-CSF is a human GM-CSF sequence.

Expression vector for use according to any one of claims 1 to 12, wherein said expression vector further comprises a promoter.

Expression vector for use according to any one of claims 1 to 13, wherein said first insert and said second insert are operably linked to said promoter.

15. According to any one of claims 1 to 14, the expression vector further comprises a nucleic acid sequence encoding a Picornavirus 2A ribosome skipping peptide between the first and second nucleic acid inserts. , expression vectors for use.