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Cancer Immunology, Immunotherapy

, Volume 59, Issue 4, pp 519–527 | Cite as

A B-cell lymphoma vaccine using a depot formulation of interleukin-2 induces potent antitumor immunity despite increased numbers of intratumoral regulatory T cells

  • Sofía Grille
  • Andreína Brugnini
  • Martha Nese
  • Esteban Corley
  • Frank W. Falkenberg
  • Daniela Lens
  • José A. Chabalgoity
Original Article

Abstract

Therapeutic vaccination holds great potential as complementary treatment for non-Hodgkin’s lymphoma. Here, we report that a therapeutic whole cell vaccine formulated with IL-2 adsorbed onto aluminum hydroxide as cytokine-depot formulation elicits potent antitumor immunity and induces delayed tumor growth, control of tumor dissemination and longer survival in mice challenged with A20-lymphoma. Therapeutic vaccination induced higher numbers of tumor’s infiltrating lymphocytes (CD4+ and CD8+ T cells and NK cells), and the production of IFN-γ and IL-4 by intratumoral CD4+ T cells. Further, strong tumor antigen-specific cellular responses were detected at systemic level. Both the A20-derived antigenic material and the IL-2 depot formulation were required for induction of an effective immune response that impacted on cancer progression. All mice receiving any form of IL-2, either as part of the vaccine or alone as control, showed higher numbers of CD4+CD25+/highFoxp3+ regulatory T cells (Treg) in the tumor, which might have a role in tumor progression in these animals. Nevertheless, for those animals that received the cytokine as part of the vaccine formulation, the overall effect was improved immune response and less disseminated disease, suggesting that therapeutic vaccination overcomes the potential detrimental effect of intratumoral Treg cells. Overall, the results presented here show that a simple vaccine formulation, that can be easily prepared under GMP conditions, is a promising strategy to be used in B-cell lymphoma and may have enough merit to be tested in clinical trials.

Keywords

Lymphoma Vaccine Interleukin-2 Aluminum hydroxide Regulatory T cells 

Notes

Acknowledgments

This work was partially supported by a grant from the Comisión Sectorial de Investigación Científica (CSIC). Universidad de la República. Uruguay. S. Grille was funded by a scholarship of ProInBio, Uruguay and CSIC. The authors thank Prof. Dr. Miguel Torres and Tech. Mr. Marcelo Curbelo of the Departament of Radiotherapy, Hospital de Clínicas for technical assistance. S.G. designed and performed the experiments, and analyzed data. D.L. and J.A.C. designed the experiments and analyzed data. A.B. performed the experiments, collected and analyzed data. E.C and F.W.F. contributed with vital reagents (IL-2-AL), and contributed to experimental design. M.N. analyzed the data and S.G., D.L., and J.A.C. wrote the manuscript.

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Sofía Grille
    • 1
    • 2
  • Andreína Brugnini
    • 1
    • 2
  • Martha Nese
    • 3
  • Esteban Corley
    • 4
  • Frank W. Falkenberg
    • 5
  • Daniela Lens
    • 1
  • José A. Chabalgoity
    • 2
  1. 1.Departamento Básico de Medicina, Facultad de Medicina, Hospital de ClínicasUniversidad de la RepúblicaMontevideoUruguay
  2. 2.Laboratory for Vaccine Research, Department of Biotechnology, Facultad de Medicina, Instituto de HigieneUniversidad de la RepúblicaMontevideoUruguay
  3. 3.Cátedra de Hematología, Facultad de MedicinaHospital de ClínicasMontevideoUruguay
  4. 4.PCgenBuenos AiresArgentina
  5. 5.Cires Cell and Immune Research Services GmbHDortmundGermany

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