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Combined therapeutic effect of a monoclonal anti-idiotype tumor vaccine against NeuGc-containing gangliosides with chemotherapy in a breast carcinoma model

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Abstract

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 μg of 1E10 mAb in Alum or with 150 mg/m2 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/m2 of Doxorubicin and 600 mg/m2 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.

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Abbreviations

Ab:

Antibody

Cy:

Cyclophosphamide

CyHi :

600 mg/m2

CyLo :

150 mg/m2

Dox:

Doxorubicin

ELISA:

Enzyme-linked immunosorbent assay

Id:

Idiotype

mAb:

Monoclonal antibody

NeuGc:

Neu-Glycolyl

Treg:

Regulatory T cells

s.c.:

Subcutaneous

i.p.:

Intraperitoneal

i.v.:

Intravenous

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Authors and Affiliations

  1. National Center for Laboratory Animal Breeding, Havana, Cuba

    D. Fuentes & A. Garcia

  2. Experimental Immunotherapy Department, Center of Molecular Immunology, P.O. Box 16040, 11600, Havana, Cuba

    J. Avellanet, A. M. Vazquez, R. Perez & E. Montero

  3. Pathology Department, Hermanos Ameijeiras Hospital, Havana, Cuba

    N. Iglesias

  4. Laboratory of Molecular Oncology, Quilmes National University, Buenos Aires, Argentina

    M. R. Gabri & D. F. Alonso

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  1. D. Fuentes
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  2. J. Avellanet
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  3. A. Garcia
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  4. N. Iglesias
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  5. M. R. Gabri
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  6. D. F. Alonso
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  7. A. M. Vazquez
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  8. R. Perez
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  9. E. Montero
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Correspondence to E. Montero.

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Fuentes, D., Avellanet, J., Garcia, A. et al. Combined therapeutic effect of a monoclonal anti-idiotype tumor vaccine against NeuGc-containing gangliosides with chemotherapy in a breast carcinoma model. Breast Cancer Res Treat 120, 379–389 (2010). https://doi.org/10.1007/s10549-009-0399-9

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