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

Antoun Toubaji, Moujahed Achtar, Maurizio Provenzano, Vincent E. Herrin, Robert Behrens, Michael Hamilton, Sarah Bernstein, David Venzon, Barry Gause, Francesco Marincola, Samir N. Khleif

Research output: Contribution to journalArticle

71 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1413-1420
Number of pages8
JournalCancer Immunology, Immunotherapy
Volume57
Issue number9
DOIs
StatePublished - Sep 1 2008

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Subunit Vaccines
Pancreatic Neoplasms
Colorectal Neoplasms
Vaccines
Immunotherapy
Disease-Free Survival
Survival
Therapeutics
Pancreatic Diseases
Phase II Clinical Trials
Peptides
Cancer Vaccines
Therapeutic Uses
Immunosuppressive Agents
Real-Time Polymerase Chain Reaction
Vaccination
Messenger RNA
Mutation
Neoplasms

Keywords

  • Adjuvant
  • Colorectal cancer
  • Immunotherapy
  • Mutant ras
  • Pancreatic cancer

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

Cite this

Toubaji, A., Achtar, M., Provenzano, M., Herrin, V. E., Behrens, R., Hamilton, M., ... Khleif, S. N. (2008). Pilot study of mutant ras peptide-based vaccine as an adjuvant treatment in pancreatic and colorectal cancers. Cancer Immunology, Immunotherapy, 57(9), 1413-1420. https://doi.org/10.1007/s00262-008-0477-6

Pilot study of mutant ras peptide-based vaccine as an adjuvant treatment in pancreatic and colorectal cancers. / Toubaji, Antoun; Achtar, Moujahed; Provenzano, Maurizio; Herrin, Vincent E.; Behrens, Robert; Hamilton, Michael; Bernstein, Sarah; Venzon, David; Gause, Barry; Marincola, Francesco; Khleif, Samir N.

In: Cancer Immunology, Immunotherapy, Vol. 57, No. 9, 01.09.2008, p. 1413-1420.

Research output: Contribution to journalArticle

Toubaji, A, Achtar, M, Provenzano, M, Herrin, VE, Behrens, R, Hamilton, M, Bernstein, S, Venzon, D, Gause, B, Marincola, F & Khleif, SN 2008, 'Pilot study of mutant ras peptide-based vaccine as an adjuvant treatment in pancreatic and colorectal cancers', Cancer Immunology, Immunotherapy, vol. 57, no. 9, pp. 1413-1420. https://doi.org/10.1007/s00262-008-0477-6
Toubaji, Antoun ; Achtar, Moujahed ; Provenzano, Maurizio ; Herrin, Vincent E. ; Behrens, Robert ; Hamilton, Michael ; Bernstein, Sarah ; Venzon, David ; Gause, Barry ; Marincola, Francesco ; Khleif, Samir N. / Pilot study of mutant ras peptide-based vaccine as an adjuvant treatment in pancreatic and colorectal cancers. In: Cancer Immunology, Immunotherapy. 2008 ; Vol. 57, No. 9. pp. 1413-1420.
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AU - Behrens, Robert

AU - Hamilton, Michael

AU - Bernstein, Sarah

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N2 - 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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