OX40 triggering concomitant to IL12-engineered cell vaccine hampers the immunoprevention of HER2/neu-driven mammary carcinogenesis

Patrizia Nanni, Carla De Giovanni, Alessia Burocchi, Giordano Nicoletti, Lorena Landuzzi, Arianna Palladini, Marianna Lucia Ianzano, Ivano Arioli, Mario P Colombo, Pier-Luigi Lollini

Research output: Contribution to journalArticle

Abstract

This study evaluated the effects of combining an OX40 agonistic antibody (aOX40) with a cell vaccine targeting HER2/neu, called "Triplex". Such HER2/neu cell vaccine included two biological adjuvants (interleukin 12 (IL12) and allogeneic histocompatibility antigens) and was previously found able to prevent autochthonous HER2/neu-driven mammary carcinogenesis. Timing of aOX40 administration, concomitantly or after cell vaccination, gave opposite results. Unexpectedly, vaccine efficacy was hampered by concomitant OX40 triggering. Such decreased immunoprevention was likely due to a reduced induction of anti-HER2/neu antibodies and to a higher level of Treg activation. On the contrary, aOX40 administration after the completion of vaccination slightly but significantly increased immunopreventive vaccine efficacy, and led to increased production of GM-CSF and IL10. In conclusion, OX40 triggering can either impair or ameliorate immunoprevention of HER2/neu-driven mammary carcinogenesis depending on the schedule of aOX40 administration.

Original languageEnglish
Pages (from-to)e1465164
JournalOncoImmunology
Volume7
Issue number8
DOIs
Publication statusPublished - 2018

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Interleukin-12
Carcinogenesis
Breast
Vaccines
Vaccination
Histocompatibility Antigens
Antibodies
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-10
Appointments and Schedules

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OX40 triggering concomitant to IL12-engineered cell vaccine hampers the immunoprevention of HER2/neu-driven mammary carcinogenesis. / Nanni, Patrizia; De Giovanni, Carla; Burocchi, Alessia; Nicoletti, Giordano; Landuzzi, Lorena; Palladini, Arianna; Ianzano, Marianna Lucia; Arioli, Ivano; Colombo, Mario P; Lollini, Pier-Luigi.

In: OncoImmunology, Vol. 7, No. 8, 2018, p. e1465164.

Research output: Contribution to journalArticle

Nanni, Patrizia ; De Giovanni, Carla ; Burocchi, Alessia ; Nicoletti, Giordano ; Landuzzi, Lorena ; Palladini, Arianna ; Ianzano, Marianna Lucia ; Arioli, Ivano ; Colombo, Mario P ; Lollini, Pier-Luigi. / OX40 triggering concomitant to IL12-engineered cell vaccine hampers the immunoprevention of HER2/neu-driven mammary carcinogenesis. In: OncoImmunology. 2018 ; Vol. 7, No. 8. pp. e1465164.
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abstract = "This study evaluated the effects of combining an OX40 agonistic antibody (aOX40) with a cell vaccine targeting HER2/neu, called {"}Triplex{"}. Such HER2/neu cell vaccine included two biological adjuvants (interleukin 12 (IL12) and allogeneic histocompatibility antigens) and was previously found able to prevent autochthonous HER2/neu-driven mammary carcinogenesis. Timing of aOX40 administration, concomitantly or after cell vaccination, gave opposite results. Unexpectedly, vaccine efficacy was hampered by concomitant OX40 triggering. Such decreased immunoprevention was likely due to a reduced induction of anti-HER2/neu antibodies and to a higher level of Treg activation. On the contrary, aOX40 administration after the completion of vaccination slightly but significantly increased immunopreventive vaccine efficacy, and led to increased production of GM-CSF and IL10. In conclusion, OX40 triggering can either impair or ameliorate immunoprevention of HER2/neu-driven mammary carcinogenesis depending on the schedule of aOX40 administration.",
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T1 - OX40 triggering concomitant to IL12-engineered cell vaccine hampers the immunoprevention of HER2/neu-driven mammary carcinogenesis

AU - Nanni, Patrizia

AU - De Giovanni, Carla

AU - Burocchi, Alessia

AU - Nicoletti, Giordano

AU - Landuzzi, Lorena

AU - Palladini, Arianna

AU - Ianzano, Marianna Lucia

AU - Arioli, Ivano

AU - Colombo, Mario P

AU - Lollini, Pier-Luigi

PY - 2018

Y1 - 2018

N2 - This study evaluated the effects of combining an OX40 agonistic antibody (aOX40) with a cell vaccine targeting HER2/neu, called "Triplex". Such HER2/neu cell vaccine included two biological adjuvants (interleukin 12 (IL12) and allogeneic histocompatibility antigens) and was previously found able to prevent autochthonous HER2/neu-driven mammary carcinogenesis. Timing of aOX40 administration, concomitantly or after cell vaccination, gave opposite results. Unexpectedly, vaccine efficacy was hampered by concomitant OX40 triggering. Such decreased immunoprevention was likely due to a reduced induction of anti-HER2/neu antibodies and to a higher level of Treg activation. On the contrary, aOX40 administration after the completion of vaccination slightly but significantly increased immunopreventive vaccine efficacy, and led to increased production of GM-CSF and IL10. In conclusion, OX40 triggering can either impair or ameliorate immunoprevention of HER2/neu-driven mammary carcinogenesis depending on the schedule of aOX40 administration.

AB - This study evaluated the effects of combining an OX40 agonistic antibody (aOX40) with a cell vaccine targeting HER2/neu, called "Triplex". Such HER2/neu cell vaccine included two biological adjuvants (interleukin 12 (IL12) and allogeneic histocompatibility antigens) and was previously found able to prevent autochthonous HER2/neu-driven mammary carcinogenesis. Timing of aOX40 administration, concomitantly or after cell vaccination, gave opposite results. Unexpectedly, vaccine efficacy was hampered by concomitant OX40 triggering. Such decreased immunoprevention was likely due to a reduced induction of anti-HER2/neu antibodies and to a higher level of Treg activation. On the contrary, aOX40 administration after the completion of vaccination slightly but significantly increased immunopreventive vaccine efficacy, and led to increased production of GM-CSF and IL10. In conclusion, OX40 triggering can either impair or ameliorate immunoprevention of HER2/neu-driven mammary carcinogenesis depending on the schedule of aOX40 administration.

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