# US 2008/0187513 A1 · Treatment of Solid Cancers > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2008/0187513 A1 - Document ID: US20080187513A1 - Status: Published application - Kind: A1 - Application number: 11/792,264 - Filed: 2005-12-02 - Published: 2008-08-07 - Earliest claimed: 2004-12-13 - Assignees: Peplin Research Pty. Ltd. - Inventors: Steven Martin Ogbourne; Andreas Suhrbier - Web page: https://patentgrep.com/patent/US20080187513A1 ## CPC - A61K 31/22: of acyclic acids, e.g. pravastatin - A61K 36/47: Euphorbiaceae (Spurge family), e.g. Ricinus (castorbean) - A61P 35/00: Antineoplastic agents - A61P 35/04: specific for metastasis - A61P 37/04: Immunostimulants - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention relates generally to the field of cancer including tumor therapy. More particularly, the present invention relates to the treatment of solid cancers, including solid tumors, and the prevention or reduction of cancer metastasis, by chemoablation of cancer cells by an agent which also stimulates the generation of cancer-specific T-cells, a process referred to herein as immunostimulatory chemoablation. The present invention further contemplates combination therapy comprising immunostimulatory chemoablation and one or more other therapeutic regimens, which enhance, co-operate and/or synergize with the cancer-specific T-cells induced by the chemoablation. The present invention also relates to pharmaceutical compositions for use in treating cancers. ## Claims ### Claim 1 A method for treating or preventing cancer growth and/or metastasis in a subject, said method comprising administering directly or proximally to said cancer, one or more angeloyl substituted ingenanes in an amount effective to induce necrosis in at least the cancer cells and to stimulate the generation of cancer-specific T-cells. ### Claim 2 (depends on 1) The method of claim 1 wherein the cancer-specific T-cell is a CD8+ T-cell or a precursor or subset thereof. ### Claim 3 (depends on 1) The method of claim 1 wherein the cancer-specific T-cell is a CD4+ T-cell or a precursor or subset thereof. ### Claim 4 (depends on 1) The method of claim 1 further comprising the administration of an agent or therapy which enhances, co-operates and/or synergizes the cancer-specific T-cells induced following treatment with the angeloyl substituted ingenane. ### Claim 5 (depends on 1) The method of claim 1 wherein said angeloyl substituted ingenane is derived from a plant of the Euphorbiaceae family or botanical or horticultural relatives of such plants. ### Claim 6 (depends on 5) The method of claim 5 wherein the angeloyl substituted ingenane is derived from E. peplus. ### Claim 7 (depends on 6) The method of claim 6 wherein the angeloyl substitute ingenane is selected from the group consisting of ingenol-3-angelate, 20-deoxy-ingenol-3-angelate, 20-O-acetyl-ingenol-3-angelate, or derivatives of said angelates, or pharmaceutically acceptable salts of these. ### Claim 8 (depends on 7) The method of claim 7 wherein the angeloyl substituted ingenane is ingenol-3-angelate. ### Claim 9 (depends on 4) The method of claim 4 wherein said agent is a cancer vaccine. ### Claim 10 (depends on 4) The method of claim 4 wherein said agent is a cytokine or cocktail of cytokines. ### Claim 11 (depends on 10) The method of claim 10 wherein the cytokine is IL-2, IL-7 and/or IL-15. ### Claim 12 (depends on 9) The method of claim 9 wherein said cancer vaccine comprises a DC vaccine. ### Claim 13 (depends on 9) The method of claim 9 wherein said cancer vaccine comprises a cancer vaccine containing or encoding a cancer antigen or epitope. ### Claim 14 (depends on 1) The method of claim 1 wherein the cancer is selected from the list consisting of AIDS related cancer, acoustic neoma, adenocystic carcinoma, adrenocortical cancer, agnogenic myeloid metaplasia, alopecia, alveolar soft-part sarcoma, anal cancer, angiosarcoma, aplastic anaemia, astrocytoma, ataxia-telangiectasia, basal cell carcinoma (bcc), bladder cancer, bone cancers, bowel cancer, brain stem glioma, brain and CNS cancers, breast cancer, CNS cancers, carcinoid cancers, cervical cancer, childhood brain cancers, childhood cancer, childhood soft tissue sarcoma, chondrosarcoma, choriocarcinoma, colorectal cancers, cutaneous T-Cell lymphoma, dermatofibrosarcoma-protuberans, desmoplastic small round cell cancer, ductal carcinoma, endocrine cancers, endometrial cancer, ependymoma, esophageal cancer, Ewing's sarcoma, extra hepatic bile duct cancer, eye cancer, eye: melanoma, retinoblastoma, fallopian tube cancer, fanconi anaemia, fibrosarcoma, gall bladder cancer, gastric cancer, gastrointestinal cancers, gastrointestinal carcinoid cancer, genitourinary cancers, germ cell cancers, gestational trophoblastic disease, glioma, gynecological cancers, hematological malignancies, head and neck cancer, hepatocellular cancer, hereditary breast cancer, histiocytosis, Hodgkin's disease, human papillomavirus, hydatidiform mole, hypercalcemia, hypopharynx cancer, intra-ocular melanoma, isle T-cell cancer, Kaposi's sarcoma, kidney cancer, Langerhan's cell histiocytosis, laryngeal cancer, leiomyosarcoma, li-fraumeni syndrome, lip cancer, liposarcoma, liver cancer, lung cancer, lymphedema, lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, male breast cancer, malignant rhabdoid cancer of kidney, medulloblastoma, melanoma, merkel cell cancer, mesothelioma, metastatic cancer, mouth cancer, multiple endocrine neoplasia, mycosis fungoides, myelodysplastic syndromes, myeloma, myeloproliferative disorders, nasal cancer, nasopharyngeal cancer, nephroblastoma, neuroblastoma, neurofibromatosis, nijmegen breakage syndrome, non-melanoma skin cancer, non-small cell lung cancer (nsclc), ocular cancers, oesophageal cancer, oral cavity cancer, oropharynx cancer, osteosarcoma, ostomy ovarian cancer, pancreas cancer, paranasal cancer, parathyroid cancer, parotid gland cancer, penile cancer, peripheral neuroectodermal cancers, pituitary cancer, polycythemia vera, prostate cancer, rare cancers and associated disorders, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, rothmund Thomson syndrome, salivary gland cancer, sarcoma, schwannoma, sezary syndrome, skin cancer, small cell lung cancer (sclc), small intestine cancer, soft tissue sarcoma, spinal cord cancers, squamous cell carcinoma (scc), stomach cancer, synovial sarcoma, testicular cancer, thymus cancer, thyroid cancer, transitional cell cancer (bladder), transitional cell cancer (renal-pelvis-/-ureter), trophoblastic cancer, urethral cancer, urinary system cancer, uroplakins, uterine sarcoma, uterus cancer, vaginal Cancer, vulva cancer, Waldenstrom's macroglobulinemia and Wilms' Cancer. ### Claim 15 (depends on 14) The method of claim 14 wherein the cancer is selected from lung cancer, breast cancer, colon cancer and bladder cancer. ### Claim 16 A method for treating a secondary cancer in a subject, said method comprising administering an angeloyl substituted ingenane or a derivative thereof directly to proximal to a primary cancer in an amount effective to induce primary necrosis in at least the cancer cells and to stimulate the generation of anti-cancer-specific T-cells. ### Claim 17 (depends on 16) The method of claim 16 wherein the cancer-specific T-cell is a CD8+ T-cell or a precursor or subset thereof. ### Claim 18 (depends on 16) The method of claim 16 wherein the cancer-specific T-cell is a CD4+ T-cell or a precursor or subset thereof. ### Claim 19 (depends on 16) The method of claim 16 further comprising using the administration of an agent or therapy which enhances, co-operates or synergizes with the cancer-specific T-cells induced following treatment with the angeloyl substituted ingenane. ### Claim 20 (depends on 16) The method of claim 16 wherein said angeloyl substituted ingenane is derived from a plant of the Euphorbiaceae family or botanical or horticultural relatives of such plants. ### Claim 21 (depends on 20) The method of claim 20 wherein the angeloyl substituted ingenane is derived from E. peplus. ### Claim 22 (depends on 21) The method of claim 21 wherein the angeloyl substitute ingenane is selected from the group consisting of ingenol-3-angelate, 20-deoxy-ingenol-3-angelate, 20-O-acetyl-ingenol-3-angelate, or derivatives of said angelates, or pharmaceutically acceptable salts of these. ### Claim 23 (depends on 22) The method of claim 22 wherein the angeloyl substituted ingenane is ingenol-3-angelate. ### Claim 24 (depends on 19) The method of claim 19 wherein said agent is a cancer vaccine. ### Claim 25 (depends on 19) The method of claim 19 wherein said agent is a cytokine or cocktail of cytokines. ### Claim 26 (depends on 25) The method of claim 25 wherein the cytokine is IL-2, IL-7 and/or IL-15. ### Claim 27 (depends on 24) The method of claim 24 wherein the cancer vaccine is a DC vaccine. ### Claim 28 (depends on 24) The method of claim 24 wherein the cancer vaccine comprises a cancer vaccine containing or encoding a cancer antigen or epitope. ### Claim 29 (depends on 17) The method of claim 17 wherein the cancer is selected from the list consisting of AIDS related cancer, acoustic neoma, adenocystic carcinoma, adrenocortical cancer, agnogenic myeloid metaplasia, alopecia, alveolar soft-part sarcoma, anal cancer, angiosarcoma, aplastic anaemia, astrocytoma, ataxia-telangiectasia, basal cell carcinoma (bcc), bladder cancer, bone cancers, bowel cancer, brain stem glioma, brain and CNS cancers, breast cancer, CNS cancers, carcinoid cancers, cervical cancer, childhood brain cancers, childhood cancer, childhood soft tissue sarcoma, chondrosarcoma, choriocarcinoma, colorectal cancers, cutaneous T-Cell lymphoma, dermatofibrosarcoma-protuberans, desmoplastic small round cell cancer, ductal carcinoma, endocrine cancers, endometrial cancer, ependymoma, esophageal cancer, Ewing's sarcoma, extra hepatic bile duct cancer, eye cancer, eye: melanoma, retinoblastoma, fallopian tube cancer, fanconi anaemia, fibrosarcoma, gall bladder cancer, gastric cancer, gastrointestinal cancers, gastrointestinal carcinoid cancer, genitourinary cancers, germ cell cancers, gestational trophoblastic disease, glioma, gynecological cancers, hematological malignancies, head and neck cancer, hepatocellular cancer, hereditary breast cancer, histiocytosis, Hodgkin's disease, human papillomavirus, hydatidiform mole, hypercalcemia, hypopharynx cancer, intra-ocular melanoma, isle T-cell cancer, Kaposi's sarcoma, kidney cancer, Langerhan's cell histiocytosis, laryngeal cancer, leiomyosarcoma, li-fraumeni syndrome, lip cancer, liposarcoma, liver cancer, lung cancer, lymphedema, lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, male breast cancer, malignant rhabdoid cancer of kidney, medulloblastoma, melanoma, merkel cell cancer, mesothelioma, metastatic cancer, mouth cancer, multiple endocrine neoplasia, mycosis fungoides, myelodysplastic syndromes, myeloma, myeloproliferative disorders, nasal cancer, nasopharyngeal cancer, nephroblastoma, neuroblastoma, neurofibromatosis, nijmegen breakage syndrome, non-melanoma skin cancer, non-small cell lung cancer (nsclc), ocular cancers, oesophageal cancer, oral cavity cancer, oropharynx cancer, osteosarcoma, ostomy ovarian cancer, pancreas cancer, paranasal cancer, parathyroid cancer, parotid gland cancer, penile cancer, peripheral neuroectodermal cancers, pituitary cancer, polycythemia vera, prostate cancer, rare cancers and associated disorders, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, rothmund Thomson syndrome, salivary gland cancer, sarcoma, schwannoma, sezary syndrome, skin cancer, small cell lung cancer (sclc), small intestine cancer, soft tissue sarcoma, spinal cord cancers, squamous cell carcinoma (scc), stomach cancer, synovial sarcoma, testicular cancer, thymus cancer, thyroid cancer, transitional cell cancer (bladder), transitional cell cancer (renal-pelvis-/-ureter), trophoblastic cancer, urethral cancer, urinary system cancer, uroplakins, uterine sarcoma, uterus cancer, vaginal Cancer, vulva cancer, Waldenstrom's macroglobulinemia and Wilms' Cancer. ### Claim 30 (depends on 29) The method of claim 29 wherein the cancer is selected from lung cancer, breast cancer, colon cancer and bladder cancer. ### Claim 31 A pharmaceutical composition comprising an angeloyl substituted ingenane and at least one agent capable of enhancing, co-operating or synergizing with cancer-specific T-cells said composition further comprising pharmaceutically acceptable carrier, diluent or excipient. ### Claim 32 (depends on 31) The pharmaceutical composition of claim 31 wherein the angeloyl substituted ingenane is derived from a plant of the Euphorbiaceae family or botanical or horticultural relatives of such plants. ### Claim 33 (depends on 32) The pharmaceutical composition of claim 32 wherein the angeloyl substituted ingenane is derived from E. peplus. ### Claim 34 (depends on 31) The pharmaceutical composition of claim 31 wherein the angeloyl substituted ingenane is synthetically produced. ### Claim 35 (depends on 31) The pharmaceutical composition of claim 31 wherein the angeloyl substituted ingenane is selected from the group consisting of ingenol-3-angelate, 20-deoxy-ingenol-3-angelate, 20-O-acetyl-ingenol-3-angelate, or derivatives of said angelates, or pharmaceutically acceptable salts of these. ### Claim 36 (depends on 35) The pharmaceutical composition of claim 35 wherein the angeloyl substituted ingenane is ingenol-3-angelate. ### Claim 37 (depends on 33) The pharmaceutical composition of claim 33 wherein said pharmaceutical composition is suitable for local administration. ### Claim 38 (depends on 31) The composition of claim 31 wherein said agent is a cancer vaccine. ### Claim 39 (depends on 31) The composition of claim 31 wherein said agent is a cytokine or cocktail of cytokines. ### Claim 40 (depends on 39) The composition of claim 39 wherein the cytokine is IL-2, IL-7 and/or IL-15. ### Claim 41 (depends on 38) The composition of claim 38 wherein the cancer vaccine is a DC vaccine. ### Claim 42 (depends on 38) The composition of claim 38 wherein the cancer vaccine comprises a cancer vaccine containing or encoding a cancer antigen or epitope. ### Claim 43 (canceled) ### Claim 44 (canceled)