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Twelve-year survival and immune correlates in dendritic cell–vaccinated melanoma patients
Stefanie Gross, … , Gerold Schuler, Beatrice Schuler-Thurner
Stefanie Gross, … , Gerold Schuler, Beatrice Schuler-Thurner
Published April 20, 2017
Citation Information: JCI Insight. 2017;2(8):e91438. https://doi.org/10.1172/jci.insight.91438.
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Clinical Medicine Clinical trials Vaccines

Twelve-year survival and immune correlates in dendritic cell–vaccinated melanoma patients

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Abstract

Background. Reports on long-term (≥10 years) effects of cancer vaccines are missing. Therefore, in 2002, we initiated a phase I/II trial in cutaneous melanoma patients to further explore the immunogenicity of our DC vaccine and to establish its long-term toxicity and clinical benefit after a planned 10-year followup.

Methods. Monocyte-derived DCs matured by TNFα, IL-1β, IL-6, and PGE2 and then loaded with 4 HLA class I and 6 class II–restricted tumor peptides were injected intradermally in high doses over 2 years. We performed serial immunomonitoring in all 53 evaluable patients.

Results. Vaccine-specific immune responses including high-affinity, IFNγ-producing CD4+ and lytic polyfunctional CD8+ T cells were de novo induced or boosted in most patients. Exposure of mature DCs to trimeric soluble CD40 ligand, unexpectedly, did not further enhance such immune responses, while keyhole limpet hemocyanin (KLH) pulsing to provide unspecific CD4+ help promoted CD8+ T cell responses — notably, their longevity. An unexpected 19% of nonresectable metastatic melanoma patients are still alive after 11 years, a survival rate similar to that observed in ipilimumab-treated patients and achieved without any major (>grade 2) toxicity. Survival correlated significantly with the development of intense vaccine injection site reactions, and with blood eosinophilia after the first series of vaccinations, suggesting that prolonged survival was a consequence of DC vaccination.

Conclusions. Long-term survival in advanced melanoma patients undergoing DC vaccination is similar to ipilimumab-treated patients and occurs upon induction of tumor-specific T cells, blood eosinophilia, and strong vaccine injection site reactions occurring after the initial vaccinations.

TRIAL REGISTRATION. ClinicalTrials.gov NCT00053391.

FUNDING. European Community, Sixth Framework Programme (Cancerimmunotherapy LSHC-CT-2006-518234; DC-THERA LSHB-CT-2004-512074), and German Research Foundation (CRC 643, C1, Z2).

Authors

Stefanie Gross, Michael Erdmann, Ina Haendle, Steve Voland, Thomas Berger, Erwin Schultz, Erwin Strasser, Peter Dankerl, Rolf Janka, Stefan Schliep, Lucie Heinzerling, Karl Sotlar, Pierre Coulie, Gerold Schuler, Beatrice Schuler-Thurner

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Figure 1

Study scheme.

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Study scheme.
(A) Leukaphereses were performed before trial start and th...
(A) Leukaphereses were performed before trial start and then repeated after 3 months, 1 year, and 2 years. Vaccinations were given in increasing intervals of 2 weeks to 6 months. Clinical evaluations were performed every 3 months. (B) CONSORT 2010 flow chart describing patient numbers for enrollment, induction, and maintenance phase of the trial, as well as trial completion.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

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