A B-cell lymphoma vaccine using a depot formulation of interleukin-2 induces potent antitumor immunity despite increased numbers of intratumoral regulatory T cells |
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Authors: | Sofía Grille Andreína Brugnini Martha Nese Esteban Corley Frank W Falkenberg Daniela Lens José A Chabalgoity |
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Institution: | 1. Departamento Básico de Medicina, Facultad de Medicina, Hospital de Clínicas, Universidad de la República, Montevideo, Uruguay 2. Laboratory for Vaccine Research, Department of Biotechnology, Facultad de Medicina, Instituto de Higiene, Universidad de la República, Montevideo, Uruguay 3. Cátedra de Hematología, Facultad de Medicina, Hospital de Clínicas, Montevideo, Uruguay 4. PCgen, Buenos Aires, Argentina 5. Cires Cell and Immune Research Services GmbH, Dortmund, Germany
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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. |
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