The Combination of ISCOMATRIX Adjuvant and TLR Agonists Induces Regression of Established Solid Tumors In Vivo
| Autor: | Matthew P. Hardy, Catherine M. Owczarek, Adele Mount, David Pejoski, Karoline Krstevska, Eugene Maraskovsky, Anabel Silva, Pierre Scotney, Adriana Baz Morelli |
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| Rok vydání: | 2015 |
| Předmět: |
Cytotoxicity
Immunologic Male Agonist Skin Neoplasms medicine.drug_class medicine.medical_treatment Immunology Melanoma Experimental CD8-Positive T-Lymphocytes Biology Cancer Vaccines Mice Immune system Adjuvants Immunologic Cancer immunotherapy medicine Animals Humans Immunology and Allergy Phospholipids Mice Knockout Melanoma Prostatic Neoplasms TLR9 Cancer Saponins medicine.disease Survival Analysis Toll-Like Receptor 3 Tumor Burden Pancreatic Neoplasms Drug Combinations Cholesterol Poly I-C Oligodeoxyribonucleotides Toll-Like Receptor 9 Immunotherapy Adjuvant Neoplasm Transplantation CD8 |
| Zdroj: | The Journal of Immunology. 194:2199-2207 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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