Prime-Boost Vaccination with SA-4-1BBL Costimulatory Molecule and Survivin Eradicates Lung Carcinoma in CD8+ T and NK Cell Dependent Manner
| Autor: | Esma S. Yolcu, Haval Shirwan, Vahap Ulker, Abhishek K. Srivastava, Gunes Dinc, Rajesh K. Sharma, Kathryn J. MacLeod |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
CD4-Positive T-Lymphocytes
Lung Neoplasms Survivin medicine.medical_treatment Cancer Treatment lcsh:Medicine CD8-Positive T-Lymphocytes Inhibitor of Apoptosis Proteins Mice chemistry.chemical_compound 0302 clinical medicine Cytotoxic T cell lcsh:Science 0303 health sciences Multidisciplinary Vaccination DNA Neoplasm Recombinant Proteins 3. Good health Killer Cells Natural Treatment Outcome Oncology 030220 oncology & carcinogenesis Medicine Immunotherapy Cancer Prevention Adjuvant Research Article Tumor Immunology Immunology Immunization Secondary Biology Cancer Vaccines 03 medical and health sciences Immune system medicine Animals Autoantibodies 030304 developmental biology lcsh:R Immunity Immunologic Subspecialties Vaccine efficacy Mice Inbred C57BL Repressor Proteins 4-1BB Ligand 4-1BB ligand Immunization chemistry lcsh:Q Clinical Immunology CD8 |
| Zdroj: | PLoS ONE PLoS ONE, Vol 7, Iss 11, p e48463 (2012) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0048463 |
| Popis: | Subunit vaccines containing universal tumor associated antigens (TAAs) present an attractive treatment modality for cancer primarily due to their safety and potential to generate long-term immunological responses that can safeguard against recurrences. However, TAA-based subunit vaccines require potent adjuvants for therapeutic efficacy. Using a novel form of the 4-1BBL costimulatory molecule, SA-4-1BBL, as the adjuvant of choice, we previously demonstrated that a single vaccination with survivin (SVN) as a bona fide self TAA was effective in eradicating weakly immunogenic 3LL tumors in >70% of C57BL/6 mice. The present study was designed to i) assess the therapeutic efficacy of a prime-boost vaccination and ii) investigate the mechanistic basis of vaccine efficacy. Our data shows that a prime-boost vaccination strategy was effective in eradicating 3LL lung carcinoma in 100% of mice. The vaccine efficacy was correlated with increased percentages of CD8(+) T cells expressing IFN-γ as well as potent killing responses of both CD8(+) T and NK cells in the absence of detectable antibodies to ssDNA as a sign of autoimmunity. Antibody depletion of CD8(+) T cells one day before vaccination completely abrogated therapeutic efficacy, whereas depletion of CD4(+) T cells had no effect. Importantly, NK cell depletion had a moderate (∼50% reduction), but significant (p |
| Databáze: | OpenAIRE |
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