Complete antitumor protection by perioperative immunization with GM3/VSSP vaccine in a preclinical mouse melanoma model

MR GABRI; Z MAZORRA; GV RIPOLL; C MESA; LE FERNANDEZ; DE GOMEZ; DF ALONSO

CLINICAL CANCER RESEARCH

Año: 2006 vol. 12 p. 7092 - 7098

1078-0432

PURPOSE: The GM3/VSSP vaccine is composed of very small sized proteoliposomes resulting from the hydrophobic conjugation of GM3 ganglioside with membrane proteins from Neisseria meningitidis. Previously, we showed that preventive vaccination with GM3/VSSP induces a specific antitumor response and elicits the rejection of syngeneic GM3-positive melanoma cells in immunized mice. Our aim was to explore the antitumor properties of perioperative GM3/VSSP vaccination in a preclinical mouse model. EXPERIMENTAL DESIGN: The highly metastatic B16F10 mouse melanoma was used to investigate perioperative vaccination with GM3/VSSP. The vaccine was administered i.m. in doses of 120 microg emulsified with the adjuvant Montanide ISA 51 at weekly or biweekly intervals, and s.c. tumors were excised 25 to 31 days after tumor cell implantation. The persistence of antitumor protection and dose dependency was also examined in preimmunized animals. To evaluate the immune performance of tumor-bearing and tumor-operated mice, ovoalbumin-specific delayed-type hypersensitivity, cytokine secretion, and cell proliferation responses were studied. RESULTS: Surgical excision of B16F10 tumors improved survival, and perioperative immunization with four biweekly GM3/VSSP doses yielded survival for all animals (P = 0.04; log-rank test). Mice showed neither local recurrence nor lung metastasis at the end of the experiment. An impairment of CD4(+) T-cell responses was observed in tumor-bearing animals measured as neoantigen-specific delayed-type hypersensitivity, with a significant recovery after surgery. A strong interleukin-4 secretion was induced in B16F10-operated mice, whereas IFN-gamma remained unaffected. CONCLUSION: Preclinical evidence suggests that GM3/VSSP vaccine might have therapeutic potential to induce antitumor immunity in patients with minimal residual disease after surgery, thereby preventing or prolonging the time to recurrence.