Cancer Immunology, Immunotherapy

, Volume 60, Issue 3, pp 371–380 | Cite as

Invasion and destruction of a murine fibrosarcoma by Salmonella-induced effector CD8 T cells as a therapeutic intervention against cancer

  • Elisabeth Roider
  • Stefan Jellbauer
  • Brigitte Köhn
  • Christina Berchtold
  • Miriam Partilla
  • Dirk H. Busch
  • Holger Rüssmann
  • Klaus Panthel
Original Article
First Online:
Received:
Accepted:

Abstract

We have developed a new vaccination strategy by using the Salmonella type III secretion system (T3SS) to translocate heterologous antigens into the cytosol of host cells. This leads to an efficient antigen-specific CD8 T cell induction. Recently, we have demonstrated the use of Salmonella’s T3SS for the immunoprophylaxis of a solid tumor. The murine fibrosarcoma WEHI 164 was transfected with the DNA sequence encoding the MHC class I-peptide p60217–225 from Listeria monocytogenes. In the present study, we used this tumor model to investigate the potential of vaccination with recombinant Salmonella in a therapeutic setting. BALB/c mice were subcutaneously challenged with WEHI-p60 cells. Simultaneously or 4 days later, these mice received either an orogastric or intravenous immunization with Salmonella translocating p60. Interestingly, 71–80% of the intravenously and 50–52% of the orogastrically immunized mice showed a complete tumor regression after 14 days. In addition, the distribution of tetramer-positive p60217–225-specific CD8 T cell subpopulations in blood and tumor tissue was analyzed. Co-staining with CD62L and CD127 revealed that the frequencies of p60217–225-specific effector and effector memory CD8 T cells in blood and in fibrosarcoma tissue were related to the kinetics of tumor regression. In summary, our study demonstrates that therapeutic vaccination with Salmonella leads to efficient induction of tumor-invading effector CD8 T cells that may result in significant tumor regression.

Keywords

Salmonella vaccine Murine fibrosarcoma model Therapeutic anti-tumor immunity Tumor-invading effector CD8 T cells 
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Notes

Acknowledgments

This research was conducted by Elisabeth Roider in partial fulfillment of the requirements for a Ph.D. from the Ludwig-Maximilians-University, Munich, Germany. Elisabeth Roider was supported by the “Förderprogramm für Forschung und Lehre” from the Ludwig-Maximilians-University Munich. Holger Rüssmann was supported by the Deutsche Forschungsgemeinschaft (grant RU 838/1-3 and grant RU 838/2-1). Christina Berchtold was supported by the Deutsche Forschungsgemeinschaft (Graduiertenkolleg 1202 “Oligonucleotides in Cell Biology and Therapy”). Dirk H. Busch was supported by the SFB 576 (TP-A8), SFB 456 (TP-B13) and TR-SFB 36 (TP-B10/13).

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Elisabeth Roider
    • 1
  • Stefan Jellbauer
    • 1
  • Brigitte Köhn
    • 1
  • Christina Berchtold
    • 1
  • Miriam Partilla
    • 1
  • Dirk H. Busch
    • 2
    • 3
  • Holger Rüssmann
    • 4
  • Klaus Panthel
    • 1
  1. 1.Max von Pettenkofer-Institute for Hygiene and Medical MicrobiologyLudwig-Maximilians-University MunichMunichGermany
  2. 2.Institute for Medical Microbiology, Immunology and HygieneTechnical University MunichMunichGermany
  3. 3.Clinical Cooperation Group “Antigen-specific Immunotherapy”Helmholtz Center Munich and TUMNeuherbergGermany
  4. 4.Institute for Microbiology, Immunology and Laboratory MedicineHELIOS Clinic Emil von BehringBerlinGermany

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