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Combined immunization with adjuvant molecules poly(I:C) and anti-CD40 plus a tumor antigen has potent prophylactic and therapeutic antitumor effects

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Abstract

The low immunogenicity of malignant cells is one of the causes responsible for the lack of antitumor immune responses. Thus, development of new therapeutic strategies aimed at enhancing presentation of tumor antigens to T cells is a main goal of cancer immunotherapy. With this aim, we studied the efficacy of administering adjuvants poly(I:C) and agonistic anti-CD40 antibody plus a tumor antigen. Joint intravenous immunization with these adjuvants and a model tumor antigen (ovalbumin) was able to synergistically induce potent and long lasting antitumor T-cell responses. These responses protected against challenge with E.G7–OVA tumor cells in prophylactic short- and long-term vaccination. In a therapeutic setting, repeated intratumor administration of adjuvants plus antigen was able to reject established tumors in all treated animals, leading in some cases to the rejection of both locally treated and untreated tumors. Antitumor immune responses induced by these protocols were mediated not only by T-cells but also by NK cells. In conclusion, combined administration of adjuvants poly(I:C) and anti-CD40 plus a tumor antigen is an efficient strategy for prophylactic and therapeutic antitumor vaccination.

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Abbreviations

OVA:

Ovalbumin

TLR:

Toll like receptors

poly(I:C):

Polyinosinic polycytidylic acid

i.v.:

Intravenous

i.t.:

Intratumor

s.c.:

Subcutaneous

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Acknowledgments

This work was supported by grants from Ministerio de Ciencia y Tecnología (SAF2003–04751) to F.B.-C., and by “UTE project CIMA” and Instituto de Salud Carlos III (C03/02) to all authors. A. Zabaleta is recipient of a scholarship from Gobierno de Navarra. The authors thank Dr. I. Melero for his kindly gift of Rag1–/– mice.

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Authors and Affiliations

  1. Center for Applied Medical Research (CIMA), Division of Hepatology and Gene Therapy, University of Navarra, Pío XII 55, 31008, Pamplona, Spain

    Diana Llopiz, Javier Dotor, Aintzane Zabaleta, Juan J. Lasarte, Jesús Prieto, Francisco Borrás-Cuesta & Pablo Sarobe

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  1. Diana Llopiz
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Correspondence to Pablo Sarobe.

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Llopiz, D., Dotor, J., Zabaleta, A. et al. Combined immunization with adjuvant molecules poly(I:C) and anti-CD40 plus a tumor antigen has potent prophylactic and therapeutic antitumor effects. Cancer Immunol Immunother 57, 19–29 (2008). https://doi.org/10.1007/s00262-007-0346-8

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