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Pilot study of mutant ras peptide-based vaccine as an adjuvant treatment in pancreatic and colorectal cancers

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Abstract

Introduction

There is mounting evidence describing the immunosuppressive role of bulky metastatic disease, thus countering the therapeutic effects of tumor vaccine. Therefore, adjuvant immunotherapy may have a better impact on clinical outcome. In this phase II clinical trial, we aimed to test the feasibility of using a specific mutant ras peptide vaccine as an adjuvant immunotherapy in pancreatic and colorectal cancer patients.

Materials and methods

Twelve patients with no evidence of disease (NED), five pancreatic and seven colorectal cancer patients were vaccinated subcutaneously with 13-mer mutant ras peptide, corresponding to their tumor’s ras mutation. Vaccinations were given every 4 weeks, up to a total of six vaccines.

Results

No serious acute or delayed systemic side effects were seen. We detected specific immune responses to the relevant mutant ras peptide by measuring IFN-gamma mRNA expression by quantitative real-time PCR. Five out of eleven patients showed a positive immune response. Furthermore, the five pancreatic cancer patients have shown a mean disease-free survival (DFS) of 35.2+ months and a mean overall survival (OS) of 44.4+ months. The seven colorectal cancer patients have shown a mean disease-free survival (DFS) of 27.2+ months and a mean overall survival (OS) of 41.5+ months.

Conclusion

In this study, we found that it is feasible to use mutant ras vaccine in the adjuvant setting. This vaccine is safe, can induce specific immune responses, and it appears to have a positive outcome in overall survival. Therefore, we believe that such an approach warrants further investigation in combination with other therapies.

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Acknowledgments

The investigators thank Dr. Jay A. Berzofsky, Dr. Scott Abrams and Dr. Walter Urba for the valuable review of the paper.

Author information

Author notes

  1. Antoun Toubaji

    Present address: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

  2. Maurizio Provenzano

    Present address: Oncology and Tissue Engineering Sections, Department of Urology, University Hospital of Zürich, Zürich, Switzerland

  3. Vincent E. Herrin

    Present address: Division of Hematology, University of Mississippi Medical Center, Jackson, MS, USA

  4. Michael Hamilton

    Present address: Avalon Pharmaceuticals Inc, Germantown, MD, USA

Authors and Affiliations

  1. Cancer Vaccine Section, Vaccine Branch, NCI, NIH, NNMC, Bldg 8, Room 5101, 8901 Wisconsin Ave, Bethesda, MD, 20889, USA

    Antoun Toubaji, Moujahed Achtar, Robert Behrens & Samir N. Khleif

  2. Immunogenetic Section, DTM, CC, NIH, Bethesda, MD, USA

    Maurizio Provenzano & Francesco Marincola

  3. Department of Hematology/Oncology, National Naval Medical Center, Bethesda, MD, USA

    Vincent E. Herrin

  4. Medical Oncology Clinical Research Unit (MOCRU) at the NNMC, Bethesda, MD, USA

    Michael Hamilton, Sarah Bernstein & Barry Gause

  5. Biostatistics and Data Management Section, CCR, NCI, NIH, Bethesda, MD, USA

    David Venzon

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  1. Antoun Toubaji
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  11. Samir N. Khleif
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Corresponding author

Correspondence to Samir N. Khleif.

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Toubaji, A., Achtar, M., Provenzano, M. et al. Pilot study of mutant ras peptide-based vaccine as an adjuvant treatment in pancreatic and colorectal cancers . Cancer Immunol Immunother 57, 1413–1420 (2008). https://doi.org/10.1007/s00262-008-0477-6

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  • DOI: https://doi.org/10.1007/s00262-008-0477-6

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