Nano-particle vaccination combined with TLR-7 and -9 ligands triggers memory and effector CD8+ T-cell responses in melanoma patients
Article first published online: 28 AUG 2012
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
European Journal of Immunology
Volume 42, Issue 11, pages 3049–3061, November 2012
How to Cite
Goldinger, S. M., Dummer, R., Baumgaertner, P., Mihic-Probst, D., Schwarz, K., Hammann-Haenni, A., Willers, J., Geldhof, C., Prior, J. O., Kündig, T. M., Michielin, O., Bachmann, M. F. and Speiser, D. E. (2012), Nano-particle vaccination combined with TLR-7 and -9 ligands triggers memory and effector CD8+ T-cell responses in melanoma patients. Eur. J. Immunol., 42: 3049–3061. doi: 10.1002/eji.201142361
- Issue published online: 29 OCT 2012
- Article first published online: 28 AUG 2012
- Accepted manuscript online: 18 JUL 2012 01:46AM EST
- Manuscript Accepted: 9 JUL 2012
- Manuscript Revised: 15 JUN 2012
- Manuscript Received: 30 DEC 2011
- Swiss Cancer League. Grant Number: 02279–08-2008
- Swiss National Science Foundation. Grant Number: 310030–135553
- Ludwig Institute for Cancer Research
- Cancer Research Institute (USA)
- Cancer Vaccine Collaborative (USA)
- Gottfried and Julia Bangeter Foundation (Switzerland)
- Schnyder Foundation (Switzerland)
Disclaimer: Supplementary materials have been peer-reviewed but not copyedited.
Supporting Information Table 1. Baseline Characteristics of Patients
Supporting Information Table 2. Overview of Results
Supporting Information Figure 1 Trial Design. Four groups of patients received vaccinations as indicated on the right side of the figure. For each patient, the total trial duration was approximately 9 months. The screening period took up to 4 weeks. The treatment phase, including the seven injections with MelQbG10, lasted 18 weeks and the follow-up phase ended after 36 weeks. All s.c. and i.d. injections were performed in the upper arm left or right alternatively. Injections with IFA were prepared by mixing equal volumes of MelQbG10 with IFA until the two liquids formed a homogenous emulsion. The intranodal injections were performed always in the same inguinal lymph node region. The lymph node dissected region was omitted for vaccine injections. No immunosuppressive medication was used during the study.
Supporting Information Figure 2 Anti-Melan-A and anti-Qb IgG Antibody responses. Geometric mean titers are expressed as reciprocal serum dilutions giving half-optical density in ELISA. Before vaccination (Visit 1) and at study end (Visit 12) anti-Melan A ( ♦) and anti-Qb (◊) titers were measured in patients’ blood serum samples. Panel A shows the titers of group I (1mg MelQbG10 + IFA s.c.), Panel B of group II (1mg MelQbG10 + IFA s.c. + Imiquimod 5%), Panel C of group III (1mg MelQbG10 i.d.+ Imiquimod 5%), and Panel D of group IV (14/42/140mg MelQbG10 i.n.). Mann-Whitney pair wise comparisons were performed. The contrasts of Group I and II vs. Group III and IV were statistically significant for anti-Melan-A and anti-Qb titers (p=0.003 and p=0.001, respectively).
Supporting Information Figure 3 Frequency and memory-/effector-phenotypes of Melan-A specific T cells. Results before vaccination (Prevacc) and of a single time point after vaccination with MelQbG10 (six vaccinations), from the same experiments as those for Figures 2 and 3, shown in a similar fashion. Statistical significances have been determined by the Mann-Whitney test. Where significant, P-values are symbolized with ** or * for < 0.01 or 0.01–0.049, respectively.
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