INVESTIGADORES
ALONSO Daniel Fernando
artículos
Título:
Direct validation of NGcGM3 ganglioside as a new target for cancer immunotherapy
Autor/es:
M LABRADA; M CLAVELL; Y BEBELAGUA; J LEON; DF ALONSO; MR GABRI; RC VELOSO; V VEREZ; LE FERNANDEZ
Revista:
EXPERT OPINION ON BIOLOGICAL THERAPY
Editorial:
INFORMA HEALTHCARE
Referencias:
Año: 2010 vol. 10 p. 153 - 162
ISSN:
1471-2598
Resumen:
OBJECTIVE:
The target concept means not only an aberrant
expression of a particular molecule in tumour tissues but also evidence
of a clear therapeutic advantage, as a consequence of
immune-intervention, in an antigen-positive relevant tumour model. Since
we reported the presence of NGcGM3 ganglioside in human breast tumours
years ago and though Phase I clinical trials of a ganglioside containing
vaccine have been conducted, a definitive direct validation of this
peculiar molecule as target for cancer immunotherapy has remained
unperformed.
METHODS:
Two animal models were used:
leghorn chickens and C57BL/6 mice. The murine 3LL-D122 cell line, the
derived subcutaneous tumours and metastatic lung lesions were processed
for gangliosides identification. Active immunotherapy experiments in the
3LL-D122 spontaneous lung metastasis model were performed with
NGcGM3/VSSP vaccine prepared by conjugation of NGcGM3 with the outer
membrane proteins of Neisseria meningitides.
RESULTS:
The
3LL-D122 Lewis lung carcinoma results were consistent with an increased
expression of NGcGM3 from primary tumours to metastatic lesions, as
observed in human breast cancer samples. Both vaccines, prepared with
synthetic or natural-source-derived ganglioside, showed similar
anti-tumour and immunogenicity profiles. Finally, a clear involvement of
NK1.1(+) cells and CD8(+) T cells in the anti-metastatic effect
elicited by the vaccine was manifested.
CONCLUSIONS:
While
'proof of concept' Phase II and III clinical trials with the
NGcGM3/VSSP vaccine in cancer patients are currently ongoing these
results reasonably sustain the validation of this peculiar ganglioside
as a novel target for cancer immunotherapy.