A CpG-loaded tumor cell vaccine induces antitumor CD4+ T cells that are effective in adoptive therapy for large and established tumors
| Autor: | Shoshana Levy, Matthew J. Goldstein, Ranjani Rajapaksa, Bindu Varghese, Debra K. Czerwinski, Joshua Brody, Ronald Levy, Holbrook E Kohrt |
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| Rok vydání: | 2011 |
| Předmět: |
CD4-Positive T-Lymphocytes
Adoptive cell transfer Lung Neoplasms Lymphoma medicine.medical_treatment Immunology Antigen-Presenting Cells Biology Cancer Vaccines Immunotherapy Adoptive Biochemistry Mice Phagocytosis Immunity Tumor Cells Cultured medicine Animals Antigen-presenting cell Immunobiology Mice Inbred BALB C Vaccination TLR9 Cell Biology Hematology Immunotherapy Flow Cytometry medicine.disease Tumor antigen Mice Inbred C57BL Colonic Neoplasms CpG Islands Female CD8 T-Lymphocytes Cytotoxic |
| Zdroj: | Blood. 117:118-127 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | We designed a whole tumor cell vaccine by “loading” lymphoma tumor cells with CG-enriched oligodeoxynucleotide (CpG), a ligand for the Toll-like receptor 9 (TLR9). CpG-loaded tumor cells were phagocytosed, delivering both tumor antigen(s) and the immunostimulatory CpG molecule to antigen-presenting cells (APCs). These APCs then expressed increased levels of costimulatory molecules and induced T-cell immunity. TLR9 was required in the APCs but not in the CpG-loaded tumor cell. We demonstrate that T cells induced by this vaccine are effective in adoptive cellular therapy for lymphoma. T cells from vaccinated mice transferred into irradiated, syngeneic recipients protected against subsequent lymphoma challenge and, remarkably, led to regression of large and established tumors. This therapeutic effect could be transferred by CD4+ but not by CD8+ T cells. A CpG-loaded whole-cell vaccination is practical and has strong potential for translation to the clinical setting. It is currently being tested in a clinical trial of adoptive immunotherapy for mantle-cell lymphoma. |
| Databáze: | OpenAIRE |
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