INVESTIGADORES
FAINBOIM Leonardo
artículos
Título:
Active Specific Immunotherapy of Melanoma with a GM3 Ganglioside-Based Vaccine A Report on Safety and Immunogenicity
Autor/es:
M.GUTHMANN ; R.BITTON ; A.CARNERO ; M.R.GABRI ; G.CINAT ; L.KOLIREN ; D.LEWI ; L. E. FERNANDEZ ; D. ALONSO ; D.E.GOMEZ ; L. FAINBOIM
Revista:
JOURNAL OF IMMUNOTHERAPY
Editorial:
LIPPINCOTT WILLIAMS & WILKINS
Referencias:
Lugar: Philadelphia; Año: 2004 vol. 27 p. 442 - 451
ISSN:
1524-9557
Resumen:
A novel cancer vaccine was obtained by combining GM3
ganglioside with Neisseria meningitidis outer membrane protein
complex to obtain very-small-size proteoliposomes (GM3/VSSP).
The authors report the results of a phase 1 study of intramuscular
administration of GM3/VSSP/Montanide ISA 51 to patients with
metastatic melanoma. Twenty-six patients were included in three
dose-level cohorts of 120, 240, and 360 mg. The first five doses
(induction phase) were given at 2-week intervals, and the remaining
four doses were given monthly. Patients were evaluated for doserelated
toxicities and antitumor effects. In addition, serum and peripheral
blood mononuclear cells were obtained at baseline and throughout
treatment to evaluate humoral and cellular immune responses.
One episode of severe hypotension and fever was observed in
a patient included at the highest dose level. Other toxicities consisted
of local reactions at the site of injection and mild fever and chills. Five
doses of GM3/VSSP induced an anti-GM3 IgM response in 44% of
patients. Serum reactivity was also observed against melanoma cell
lines and tumor biopsies. GM3/VSSP was shown to induce very
strong in vitro IFNg secretion in all evaluated melanoma patients.
Furthermore, in one patient IFNg secretion was shown to be GM3-
specific. A 62% reduction of a mediastinal mass was documented in
one patient (partial response), while a second patient benefited from
initial disease stabilization followed by tumor reduction in nonmeasurable
soft tissue lesions accompanied by vitiligo