Effect of vaccination with N-glycolyl GM3/VSSP vaccine by subcutaneous injection in patients with advanced cutaneous melanoma

Marta Osorio,1 Elias Gracia,1 Edmundo Reigosa,1 Julio Hernandez,2 Ana de la Torre,2 Giselle Saurez,3 Kirenia Perez,3 Carmen Viada,3 Meylán Cepeda,2 Adriana Carr,3 Yisel Ávila,4 Migdalia Rodríguez,4 Luis E Fernandez31National Institute of Oncology and Radiobiology, Havana, 2Dr Celestino Hernández Oncology Hospital, Villa Clara, 3Center of Molecular Immunology, Havana, 4National Center of Clinical Trials, Havana, CubaAbstract: NeuGc-containing gangliosides have been described in melanoma cells and are an attractive target for cancer immunotherapy because they are minimally or not expressed in normal human tissues. Melanoma patients treated with a vaccine based on N-glycolyl gangliosides have shown benefit in progression free survival and overall survival. We conducted a multicenter Phase I/II clinical trial in patients with metastatic cutaneous melanoma treated with the N-gycolyl GM3/very-small-size proteoliposomes vaccine by the subcutaneous route. Selecting the optimal biological dose of the vaccine was the principal objective based on immunogenicity, efficacy, and safety results. Six dose levels were studied and the treatment schedule consisted of five doses administered every 2 weeks and then monthly until 15 doses had been given. Dose levels evaluated were 150, 300, 600, 900, 1200, and 1500 µg with five patients included in each dose level except the 900 µg dose (n = 10). Immunogenicity was determined by antibody titers generated in patients after vaccination. Antitumor effect was measured by response criteria of evaluation in solid tumors and safety was evaluated by common toxicity criteria of adverse events. The vaccine was safe and immunogenic at all doses levels. The most frequent adverse events related to vaccination were mild to moderate injection site reactions and flu-like symptoms. Vaccination induced specific anti-NeuGcGM3 immunoglobulin M and immunoglobulin G antibody responses in all patients. Disease control (objective response or stable disease) was obtained in 38.46% of patients. Global median overall survival was 20.20 months. Two patients achieved overall survival duration of about 4 and 5 years, respectively. The 900 µg dose resulted in overall survival duration of 19.40 months and was selected as the biological optimal dose.Keywords: melanoma, clinical trial, therapeutic vaccine, ganglioside, N-glycolyl GM