Tuning formulation of multipeptide vaccination for melanoma patients at high risk of relapse

Abstract

18014 Background: Vaccination with MAGE peptides is followed by tumor regression in 10–20% of metastatic melanoma patients with detectable disease, mostly those with only SC or lymph node metastases. Anti-vaccine cytolytic T lymphocyte (CTL) responses have been observed in about 50% of the regressor patients, suggesting that these vaccines were poorly immunogenic. Recent reports have documented convincing CTL responses in patients vaccinated with peptides administered in a water-in-oil emulsion with Montanide, a clinical grade incomplete Freund’s adjuvant. After SC injection, this vaccine stimulates a local inflammation which could help to the recruitment of peptide presenting cells. Considering the absence of an effective treatment to prevent relapses of cutaneous melanoma, we applied this vaccination modality in an adjuvant setting. Methods and Results: We vaccinated 14 HLA-A2 melanoma patients with no evidence of disease but at high risk of relapse, with 4 antigenic peptides (MAGE-3.A2, NA17.A2, Tyrosinase.A2 and gp100.A2) emulsified in Montanide ISA51. Seven patients received 5 vaccinations, every 3 weeks, consisting of 4 injections of 900 μg of one peptide and 1 ml Montanide. Seven other patients received the same vaccines but with 300 μg of each peptide. Toxicity was limited to grade II, at the injection sites. Two thirds of the patients mounted a CTL response to peptide gp100.A2, and 50% to peptide NA17.A2. The lower doses of peptides were as immunogenic as the higher. Conclusions: These encouraging results indicate that this simple vaccination modality is not toxic and clearly immunogenic. We wish to formally assess the role of the immunological adjuvant Montanide in these CTL responses by vaccinating a third group of patients with the same 4 antigenic peptides without Montanide. We will also vaccinate with a mix of the 4 peptides and Montanide all injected at one site, as this will reduce the number of injections and could facilitate immunological helper effects of each peptide on the others. Finally, depending on the immunological results obtained with these two additional cohorts of patients, the best modality will be used in a larger study to evaluate clinical efficacy. No significant financial relationships to disclose.