Cancer Immunology, Immunotherapy

, Volume 63, Issue 4, pp 381–394 | Cite as

Immunologic response to the survivin-derived multi-epitope vaccine EMD640744 in patients with advanced solid tumors

  • Volker Lennerz
  • Stefanie Gross
  • Elisa Gallerani
  • Cristiana Sessa
  • Nicolas Mach
  • Steffen Boehm
  • Dagmar Hess
  • Lotta von Boehmer
  • Alexander Knuth
  • Adrian F. Ochsenbein
  • Ulrike Gnad-Vogt
  • Juergen Zieschang
  • Ulf Forssmann
  • Thomas Woelfel
  • Eckhart Kaempgen
Original Article



Survivin is a member of the inhibitor-of-apoptosis family. Essential for tumor cell survival and overexpressed in most cancers, survivin is a promising target for anti-cancer immunotherapy. Immunogenicity has been demonstrated in multiple cancers. Nonetheless, few clinical trials have demonstrated survivin-vaccine-induced immune responses.

Experimental design

This phase I trial was conducted to test whether vaccine EMD640744, a cocktail of five HLA class I-binding survivin peptides in Montanide® ISA 51 VG, promotes anti-survivin T-cell responses in patients with solid cancers. The primary objective was to compare immunologic efficacy of EMD640744 at doses of 30, 100, and 300 μg. Secondary objectives included safety, tolerability, and clinical efficacy.


In total, 49 patients who received ≥2 EMD640744 injections with available baseline- and ≥1 post-vaccination samples [immunologic-diagnostic (ID)-intention-to-treat] were analyzed by ELISpot- and peptide/MHC-multimer staining, revealing vaccine-activated peptide-specific T-cell responses in 31 patients (63 %). This cohort included the per study protocol relevant ID population for the primary objective, i.e., T-cell responses by ELISpot in 17 weeks following first vaccination, as well as subjects who discontinued the study before week 17 but showed responses to the treatment. No dose-dependent effects were observed. In the majority of patients (61 %), anti-survivin responses were detected only after vaccination, providing evidence for de novo induction. Best overall tumor response was stable disease (28 %). EMD640744 was well tolerated; local injection-site reactions constituted the most frequent adverse event.


Vaccination with EMD640744 elicited T-cell responses against survivin peptides in the majority of patients, demonstrating the immunologic efficacy of EMD640744.


Survivin EMD640744 Cancer vaccines Cancer immunotherapy 



Adverse event


Ex vivo ELISpot


Ex vivo multimer staining


Fluorescence minus one


Immunologic-diagnostic population


Immunologic-diagnostic intention-to-treat population


Safety/intention-to-treat population


ELISpot following in vitro stimulation of PBMC


Multimer staining following in vitro stimulation of PBMC


Peripheral blood mononuclear cells


Treatment-emergent adverse event



The study was sponsored by Merck KGaA Darmstadt, Germany. The authors take full responsibility for the content of this publication. The authors would like to thank the patients, the investigators, co-investigators, and study teams at each of the participating centers and at Merck KGaA, Darmstadt, Germany. The contributions of Annett Hamann, the team of the cell sorting and immunomonitoring core unit in Erlangen and Daniela Eberts (Mainz), for their excellent technical assistance, are also gratefully acknowledged. Editorial assistance in the preparation of this manuscript was provided by Paola Accalai, International Medical Press, funded by Merck KGaA, Darmstadt, Germany.

Conflict of interest

Juergen Zieschang is a Merck employee. Ulf Forssmann was a Merck employee until the end of March 2013. Ulrike Gnad-Vogt was a Merck employee from 2005 to 2009 and received consultancy fees and a travel grant from Merck from 2009 to 2011 and has been a CureVac GmbH employee since 2011. All other authors declare that they have no competing interests.

Supplementary material

262_2013_1516_MOESM1_ESM.pdf (812 kb)
Supplementary material 1 (PDF 811 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Volker Lennerz
    • 1
  • Stefanie Gross
    • 2
  • Elisa Gallerani
    • 3
  • Cristiana Sessa
    • 3
  • Nicolas Mach
    • 4
  • Steffen Boehm
    • 5
  • Dagmar Hess
    • 5
  • Lotta von Boehmer
    • 6
  • Alexander Knuth
    • 6
  • Adrian F. Ochsenbein
    • 7
  • Ulrike Gnad-Vogt
    • 8
    • 10
  • Juergen Zieschang
    • 8
  • Ulf Forssmann
    • 9
    • 11
  • Thomas Woelfel
    • 1
  • Eckhart Kaempgen
    • 2
  1. 1.III. Medical Clinic/Hematology/Oncology, Verfügungsgebäude f. Forschung and Entwicklung, University Medical Center Johannes Gutenberg University MainzMainzGermany
  2. 2.Department of DermatologyUniversity Hospital of ErlangenErlangenGermany
  3. 3.IOSI Oncology Institute of Southern SwitzerlandBellinzonaSwitzerland
  4. 4.Clinical Research Unit of the Foundation Dr. Henri Dubois-Ferrière Dinu Lipatti, Oncology CenterHôpitaux Universitaires de Genève (HUG)GenevaSwitzerland
  5. 5.Onkologie/HämatologieKantonsspitalSt. GallenSwitzerland
  6. 6.Department of OncologyUniversity Hospital ZurichZurichSwitzerland
  7. 7.Universitätsklinik und Poliklinik für Medizinische OnkologieInselspitalBernSwitzerland
  8. 8.Merck KGaADarmstadtGermany
  9. 9.Merck Serono S.A.—GenevaGenevaSwitzerland
  10. 10.CureVac GmbHFrankfurt a.M.Germany
  11. 11.Bayer Pharma AGBerlinGermany

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