Tumor Protection Following Vaccination With Low Doses of Lentivirally Transduced DCs Expressing the Self-antigen erbB2
| Autor: | Chuyan Ying, Jonathan L. Bramson, Jagdeep S. Walia, Jason Foley, Daniel H. Fowler, Vanessa I. Rasaiah, Renee Head, Nicole Buxhoeveden, Miriam E. Mossoba, Jeffrey A. Medin |
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| Rok vydání: | 2008 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male Receptor ErbB-2 Recombinant Fusion Proteins Genetic enhancement Green Fluorescent Proteins CD8-Positive T-Lymphocytes Cancer Vaccines Immunotherapy Adoptive Mice Prostate cancer Antigen Transduction Genetic Prostate Cell Line Tumor Drug Discovery medicine Genetics Animals Molecular Biology Pharmacology Mice Inbred BALB C business.industry Lentivirus Vaccination Prostatic Neoplasms Cancer Dendritic Cells Genetic Therapy Flow Cytometry medicine.disease Killer Cells Natural Mice Inbred C57BL medicine.anatomical_structure Immunology Humoral immunity Cytokines Molecular Medicine Female business Spleen CD8 |
| Zdroj: | Molecular Therapy. 16(3):607-617 |
| ISSN: | 1525-0016 |
| DOI: | 10.1038/sj.mt.6300390 |
| Popis: | Gene therapy strategies may accelerate the development of prophylactic immunotherapy against cancer. We synthesized a lentiviral (LV) vector encoding a kinase-deficient form of erbB2 (erbB2tr) to transduce murine dendritic cells (DCs) efficiently. Murine erbB2 models a clinically relevant tumor-associated self-antigen; its human homolog (HER-2/neu) is overexpressed in breast cancer and in 80% of metastatic prostate cancers. Following one infection, approximately 47% of DCs overexpressed erbB2tr. To determine whether low doses of transduced DCs could protect mice from prostate cancer cells, we performed prime/boost vaccinations with 2 x 10(3) or 2 x 10(5) erbB2tr-transduced DCs. Six weeks after vaccination, mice were simultaneously bilaterally challenged with the aggressive RM-1 prostate cancer cell line and an erbB2tr-expressing variant (RM-1-erbB2tr). Whereas control mice developed both tumors, all recipients of 2 x 10(5) erbB2tr-transduced DCs developed only wild-type RM-1 tumors. One-third of mice vaccinated with just 2 x 10(3) erbB2tr-transduced DCs also demonstrated erbB2tr-specific tumor protection. Protection against RM-1-erbB2tr tumors was associated with sustained levels of anti-erbB2tr antibody production and also correlated with erbB2tr-specific Th1 cytokine secretion. Depletion of CD4(+), CD8(+), or natural killer (NK) cells prior to tumor challenge underscored their role in mediating tumor protection. We conclude that administration of DCs expressing a self-antigen through efficient LV-based gene transfer activates cellular and humoral immunity, protecting host animals against specific tumor challenge. |
| Databáze: | OpenAIRE |
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