Pilot study of mutant ras peptide-based vaccine as an adjuvant treatment in pancreatic and colorectal cancers - PubMed (original) (raw)

Clinical Trial

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

Antoun Toubaji et al. Cancer Immunol Immunother. 2008 Sep.

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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Figures

Fig. 1

Fig. 1

Immune response against the 13-mer corresponding mutant ras. q r-t PCR on PBMCs collected before vaccination (Pre-Vax) and after three vaccinations (Post-3Vax). Y axis values represent ratio of absolute IFN-γ mRNA copy numbers obtained by mutant ras peptide stimulation relative to wild type ras peptide stimulation, normalized with b-actin. Plus symbol indicates twofold increase or more of IFN-γ mRNA copies post-vaccination

Fig. 2

Fig. 2

Disease free survival. Kaplan–Meier, estimated DFS of patients with immune response compared to patients with no immune response. P values were assessed using the exact long-rank test. DFS, disease free survival—calculated as time from the first vaccination until evidence of disease progression. Vertical lines indicate the patient is still alive at last assessment

Fig. 3

Fig. 3

Overall survival. Kaplan–Meier, estimated OS of patients with immune response compared to patients with no immune response. P values were assessed using the exact long-rank test. OS, overall survival—calculated as time from the first vaccination until death. Vertical lines indicate the patient is still alive at last assessment

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