Heterophilic NeuGcGM3 ganglioside cancer vaccine in advanced melanoma patients: Results of a phase Ib/IIa study

Abstract

NeuGcGM3 ganglioside is especially attractive because it is expressed on melanoma cells but it is minimally or not expressed at all on most normal human tissues.A Phase Ib/IIa clinical trial was carried out in patients with advanced cutaneous and ocular malignant melanomas, to evaluate immunogenicity and toxicity of an intramuscularly administered cancer vaccine and composed by NeuGcGM3 in a proteoliposome of Neisseria meningitides with Montanide ISA 51 as adjuvant.Twenty two patients were included, twelve at dose level of 200 μg and 10 at 400 μg. The first five doses were administered every other week and then monthly until 9 doses. 12 patients received additional immunizations.Vaccination induced specific anti-NeuGcGM3 IgM, IgG and IgA antibodies responses. Titers of IgM were greater for the highest vaccine doses. Vaccination also elicited DTH response in 45.5% of patients in the lower doses and 77.8% in the higher doses. Toxicities were mostly grade 1 or 2, according CTC-NCI criteria. Interestingly, 3 patients developed vitiligo at the lower dose (none in the highest dose) although the nominal antigen NeuGcGM3 is not present in melanocytes. Survival analysis was not the goal of this Phase I trial; nevertheless, the fact that seven patients are alive for more than 2 years after inclusion is noteworthy.Safety and immunogenicity with NeuGcGM3 vaccine treatment in advanced melanoma patients were established. The prognostic value of autoimmunity and the possibilities of dissociating antitumor immunity from autoimmunity deserve further research.

Molecular subtyping of metastatic melanoma based on cell ganglioside metabolism profiles

“…The incorporation of N-glycolylneuraminic acid in vivo could possibly occur from biological fluids. In fact, the presence of Neu5Gc-GM3 in melanoma surgical specimens was previously largely documented [19, 32, 49]. Moreover, melanoma cluster 1 cells were characterized by the highest levels of expression of GM3 synthase: therefore, also N-glycolylneuraminic acid could be recruited faster into GM3, in these conditions.…”

Is the “3+3” Dose-Escalation Phase I Clinical Trial Design Suitable for Therapeutic Cancer Vaccine Development? A Recommendation for Alternative Design

“…In the remaining 15 trials, only 6 reported the toxicities at the highest dose level (10 systemic toxicities). Two out of these 6 trials that reported toxicities at the highest dose level used bacterial vaccines (17, 18), and the rest used autologous (19), DNA (20), viral (21), or liposomal vaccines (22). Two toxicities occurred in the middle dose level in one trial that used a bacterial vaccine, with no further toxicity occurring when the dose was escalated (23).…”

Immunogenicity and safety of a NeuGcGM3 based cancer vaccine: Results from a controlled study in metastatic breast cancer patients.

“…Safety and immunogenicity with NeuGcGM3 vaccine treatment in advanced melanoma patients were established. 10 In the present paper, we show the result of the first randomized, multicenter, phase II trial in MBC patients. Here we evaluated the safety and immunogenicity of vaccination with NeuGcGM3/VSSP/Montanide ISA 51 in MBC women after finishing first line chemotherapy.…”