Immunotherapy with MVA-BN^sup ?^-HER2 induces HER-2-specific Th1 immunity and alters the intratumoral balance of effector and regulatory T cells
MVA-BN^sup ®^-HER2 is a new candidate immunotherapy designed for the treatment of HER-2-positive breast cancer. Here, we demonstrate that a single treatment with MVA-BN^sup ®^-HER2 exerts potent anti-tumor efficacy in a murine model of experimental pulmonary metastasis. This anti-tumor efficacy occu...
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Published in | Cancer immunology, immunotherapy Vol. 61; no. 1; p. 19 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
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Heidelberg
Springer Nature B.V
01.01.2012
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Abstract | MVA-BN^sup ®^-HER2 is a new candidate immunotherapy designed for the treatment of HER-2-positive breast cancer. Here, we demonstrate that a single treatment with MVA-BN^sup ®^-HER2 exerts potent anti-tumor efficacy in a murine model of experimental pulmonary metastasis. This anti-tumor efficacy occurred despite a strong tumor-mediated immunosuppressive environment characterized by a high frequency of regulatory T cells (T^sub reg^) in the lungs of tumor-bearing mice. Immunogenicity studies showed that treatment with MVA-BN^sup ®^-HER2 induced strongly Th1-dominated HER-2-specific antibody and T-cell responses. MVA-BN^sup ®^-HER2-induced anti-tumor activity was characterized by an increased infiltration of lungs with highly activated, HER-2-specific, CD8^sup +^CD11c^sup +^ T cells accompanied by a decrease in the frequency of T^sub reg^ cells in the lung, resulting in a significantly increased ratio of effector T cells to T^sub reg^ cells. In contrast, administration of HER2 protein formulated in Complete Freund's Adjuvant (CFA) induced a strongly Th2-biased immune response to HER-2. However, this did not lead to significant infiltration of the tumor-bearing lungs by CD8^sup +^ T cells or the decrease in the frequency of T^sub reg^ cells nor did it result in anti-tumor efficacy. In vivo depletion of CD8^sup +^ cells confirmed that CD8 T cells were required for the anti-tumor activity of MVA-BN^sup ®^-HER2. Furthermore, depletion of CD4^sup +^ or CD25^sup +^ cells demonstrated that tumor-induced T^sub reg^ cells promoted tumor growth and that CD4 effector cells also contribute to MVA-BN^sup ®^-HER2-mediated anti-tumor efficacy. Taken together, our data demonstrate that treatment with MVA-BN^sup ®^-HER2 controls tumor growth through mechanisms including the induction of Th1-biased HER-2-specific immune responses and the control of tumor-mediated immunosuppression.[PUBLICATION ABSTRACT] |
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AbstractList | MVA-BN^sup ®^-HER2 is a new candidate immunotherapy designed for the treatment of HER-2-positive breast cancer. Here, we demonstrate that a single treatment with MVA-BN^sup ®^-HER2 exerts potent anti-tumor efficacy in a murine model of experimental pulmonary metastasis. This anti-tumor efficacy occurred despite a strong tumor-mediated immunosuppressive environment characterized by a high frequency of regulatory T cells (T^sub reg^) in the lungs of tumor-bearing mice. Immunogenicity studies showed that treatment with MVA-BN^sup ®^-HER2 induced strongly Th1-dominated HER-2-specific antibody and T-cell responses. MVA-BN^sup ®^-HER2-induced anti-tumor activity was characterized by an increased infiltration of lungs with highly activated, HER-2-specific, CD8^sup +^CD11c^sup +^ T cells accompanied by a decrease in the frequency of T^sub reg^ cells in the lung, resulting in a significantly increased ratio of effector T cells to T^sub reg^ cells. In contrast, administration of HER2 protein formulated in Complete Freund's Adjuvant (CFA) induced a strongly Th2-biased immune response to HER-2. However, this did not lead to significant infiltration of the tumor-bearing lungs by CD8^sup +^ T cells or the decrease in the frequency of T^sub reg^ cells nor did it result in anti-tumor efficacy. In vivo depletion of CD8^sup +^ cells confirmed that CD8 T cells were required for the anti-tumor activity of MVA-BN^sup ®^-HER2. Furthermore, depletion of CD4^sup +^ or CD25^sup +^ cells demonstrated that tumor-induced T^sub reg^ cells promoted tumor growth and that CD4 effector cells also contribute to MVA-BN^sup ®^-HER2-mediated anti-tumor efficacy. Taken together, our data demonstrate that treatment with MVA-BN^sup ®^-HER2 controls tumor growth through mechanisms including the induction of Th1-biased HER-2-specific immune responses and the control of tumor-mediated immunosuppression.[PUBLICATION ABSTRACT] |
Author | Dalpozzo, Katie Steigerwald, Robin Laus, Reiner Delcayre, Alain Do, Lisa Rountree, Ryan B Mandl, Stefanie J Dirmeier, Ulrike Schoonmaker, Peter L Giffon, Thierry Lombardo, John R |
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Title | Immunotherapy with MVA-BN^sup ?^-HER2 induces HER-2-specific Th1 immunity and alters the intratumoral balance of effector and regulatory T cells |
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