INVESTIGADORES
ALONSO Daniel Fernando
artículos
Título:
Combined therapeutic effect of a monoclonal anti-idiotype tumor vaccine against NeuGc-containing gangliosides with chemotherapy in a breast carcinoma model
Autor/es:
D FUENTES; J AVELLANET; A GARCIA; N IGLESIAS; MR GABRI; ALONSO DF; AM VAZQUEZ; R PEREZ; E MONTERO
Revista:
BREAST CANCER RESEARCH AND TREATMENT
Editorial:
SPRINGER
Referencias:
Año: 2010 vol. 120 p. 379 - 389
ISSN:
0167-6806
Resumen:
Anti-idiotypic monoclonal antibodies (mAb) have been evaluated for
actively induced immunotherapy with encouraging results. However,
rational combination of cancer vaccines with chemotherapy may improve
the therapeutic efficacy of these two approaches used separately. The
main objective of this study was to evaluate the antitumor effect of the
co-administration of 1E10 (Racotumomab), a monoclonal anti-idiotype
tumor vaccine against an IgM mAb, named P3 that reacts specifically with
NeuGc-containing gangliosides and low-dose Cyclophosphamide in a
mammary carcinoma model. F3II tumor-bearing mice were immunized
subcutaneously with 100 microg of 1E10 mAb in Alum or with 150 mg/m(2)
of Cyclophosphamide intravenously 7 days after the tumor inoculation.
While a limited antitumor effect was induced by a single 1E10 mAb
immunization; its co-administration with low-dose Cyclophosphamide
reduced significantly the F3II mammary carcinoma growth. That response
was comparable with the co-administration of the standard high-dose
chemotherapy for breast cancer based on 60 mg/m(2) of Doxorubicin and
600 mg/m(2) of Cyclophosphamide, without toxicity signs. Combinatorial
chemo-immunotherapy promoted the CD8(+) lymphocytes tumor infiltration
and enhanced tumor apoptosis. Furthermore, 1E10 mAb immunization
potentiated the antiangiogenic effect of low-dose Cyclophosphamide.
Additionally, splenic myeloid cells Gr1(+)/CD11b(+) associated with a
suppressor phenotype were significantly reduced in F3II tumor-bearing
mice immunized with 1E10 mAb alone or in combination with low-dose
Cyclophosphamide. This data may provide a rational for
chemo-immunotherapy combinations with potential medical implications in
breast cancer.