title: The combination of ISCOMATRIX adjuvant and TLR agonists induces regression of established solid tumors in vivo.
abstract: The development of therapeutic vaccines for treatment of established cancer has proven challenging. Cancer vaccines not only need to induce a robust tumor Ag-specific immune response but also need to overcome the tolerogenic and immunosuppressive microenvironments that exist within many solid cancers. ISCOMATRIX adjuvant (ISCOMATRIX) is able to induce both tumor Ag-specific cellular and Ab responses to protect mice against tumor challenge, but this is insufficient to result in regression of established solid tumors. In the current study, we have used B16-OVA melanoma, Panc-OVA pancreatic, and TRAMP-C1 prostate cancer mouse tumor models to test therapeutic efficacy of ISCOMATRIX vaccines combined with other immune modulators. The coadministration of an ISCOMATRIX vaccine with the TLR3 agonist, polyinosinic-polycytidylic acid, and TLR9 agonist, CpG, reduced tumor growth in all tumor models and the presence of ISCOMATRIX in the formulation was critical for the therapeutic efficacy of the vaccine. This vaccine combination induced a robust and multifunctional CD8(+) T cell response. Therapeutic protection required IFN-γ and CD8(+) T cells, whereas NK and CD4(+) T cells were found to be redundant. ISCOMATRIX vaccines combined with TLR3 and TLR9 agonists represent a promising cancer immunotherapy strategy.
authors: CSL Ltd., Bio21 Institute, Melbourne, Victoria 3010, Australia.
authors: Anabel
authors: A
authors: Silva
authors: CSL Ltd., Bio21 Institute, Melbourne, Victoria 3010, Australia.
authors: Adele
authors: A
authors: Mount
authors: CSL Ltd., Bio21 Institute, Melbourne, Victoria 3010, Australia.
authors: Karoline
authors: K
authors: Krstevska
authors: CSL Ltd., Bio21 Institute, Melbourne, Victoria 3010, Australia.
authors: David
authors: D
authors: Pejoski
authors: CSL Ltd., Bio21 Institute, Melbourne, Victoria 3010, Australia.
authors: Matthew P
authors: MP
authors: Hardy
authors: CSL Ltd., Bio21 Institute, Melbourne, Victoria 3010, Australia.
authors: Catherine
authors: C
authors: Owczarek
authors: CSL Ltd., Bio21 Institute, Melbourne, Victoria 3010, Australia.
authors: Pierre
authors: P
authors: Scotney
authors: CSL Ltd., Bio21 Institute, Melbourne, Victoria 3010, Australia.
authors: Eugene
authors: E
authors: Maraskovsky
authors: CSL Ltd., Bio21 Institute, Melbourne, Victoria 3010, Australia adriana.bazmorelli@csl.com.au.
authors: Adriana
authors: A
authors: Baz Morelli
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage*; D002784:Cholesterol / Q000008:administration & dosage*; D003602:Cytotoxicity, Immunologic; D004338:Drug Combinations; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008297:Male; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D051379:Mice; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D010743:Phospholipids / Q000008:administration & dosage*; D011070:Poly I-C / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D012503:Saponins / Q000008:administration & dosage*; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D016019:Survival Analysis; D051196:Toll-Like Receptor 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D004338:Drug Combinations; C493786:ISCOMATRIX; D009838:Oligodeoxyribonucleotides; D010743:Phospholipids; D012503:Saponins; C519703:TLR3 protein, mouse; C495370:Tlr9 protein, mouse; D051196:Toll-Like Receptor 3; D051217:Toll-Like Receptor 9; D002784:Cholesterol; D011070:Poly I-C