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Cancer Immunology Research
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Research Articles

Characterization of BAY 1905254, an Immune Checkpoint Inhibitor Targeting the Immunoglobulin-Like Domain Containing Receptor 2 (ILDR2)

Julia Huetter, Uwe Gritzan, Ilona Gutcher, Wolf-Dietrich Doecke, Merlin V. Luetke-Eversloh, Sven Golfier, Helge G. Roider, Anna-Lena Frisk, John Hunter, Andrew Pow, Andrew Drake, Zurit Levine, Ofer Levy, Meir Azulay, Inbal Barbiro, Gady Cojocaru, Ilan Vaknin, Bertolt Kreft and Lars Roese
Julia Huetter
1Immuno-Oncology (Research), Pharmaceuticals Division, Bayer AG, Germany.
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Uwe Gritzan
2Global Biologics, Pharmaceuticals Division, Bayer AG, Cologne, Germany.
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Ilona Gutcher
1Immuno-Oncology (Research), Pharmaceuticals Division, Bayer AG, Germany.
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Wolf-Dietrich Doecke
3Biomarker Strategy, Pharmaceuticals Division, Bayer AG, Berlin, Germany.
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Merlin V. Luetke-Eversloh
4Biomarker Research, Pharmaceuticals Division, Bayer AG, Berlin, Germany.
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Sven Golfier
4Biomarker Research, Pharmaceuticals Division, Bayer AG, Berlin, Germany.
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Helge G. Roider
5Bioinformatics, Pharmaceuticals Division, Bayer AG, Berlin, Germany.
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Anna-Lena Frisk
1Immuno-Oncology (Research), Pharmaceuticals Division, Bayer AG, Germany.
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John Hunter
6Compugen USA Inc., South San Francisco, California.
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Andrew Pow
7New Paradigm Biosciences, Woburn, Massachusetts.
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Andrew Drake
6Compugen USA Inc., South San Francisco, California.
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Zurit Levine
8Compugen Ltd., Holon, Israel.
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Ofer Levy
8Compugen Ltd., Holon, Israel.
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Meir Azulay
8Compugen Ltd., Holon, Israel.
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Inbal Barbiro
8Compugen Ltd., Holon, Israel.
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Gady Cojocaru
8Compugen Ltd., Holon, Israel.
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Ilan Vaknin
8Compugen Ltd., Holon, Israel.
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Bertolt Kreft
1Immuno-Oncology (Research), Pharmaceuticals Division, Bayer AG, Germany.
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Lars Roese
1Immuno-Oncology (Research), Pharmaceuticals Division, Bayer AG, Germany.
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  • For correspondence: lars.roese@bayer.com
DOI: 10.1158/2326-6066.CIR-19-0321 Published July 2020
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Abstract

The immunoglobulin-like domain containing receptor 2 (ILDR2), a type I transmembrane protein belonging to the B7 family of immunomodulatory receptors, has been described to induce an immunosuppressive effect on T-cell responses. Besides its expression in several nonlymphoid tissue types, we found that ILDR2 was also expressed in fibroblastic reticular cells (FRC) in the stromal part of the lymph node. These immunoregulatory cells were located in the T-cell zone and were essential for the recruitment of naïve T cells and activated dendritic cells to the lymph nodes. Previously, it has been shown that an ILDR2-Fc fusion protein exhibits immunomodulatory effects in several models of autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and type I diabetes. Herein, we report the generation and characterization of a human/mouse/monkey cross-reactive anti-ILDR2 hIgG2 antibody, BAY 1905254, developed to block the immunosuppressive activity of ILDR2 for cancer immunotherapy. BAY 1905254 was shown to promote T-cell activation in vitro and enhance antigen-specific T-cell proliferation and cytotoxicity in vivo in mice. BAY 1905254 also showed potent efficacy in various syngeneic mouse cancer models, and the efficacy was found to correlate with increasing mutational load in the cancer models used. Additive or even synergistic antitumor effects were observed when BAY 1905254 was administered in combination with anti–PD-L1, an immunogenic cell death–inducing chemotherapeutic, or with tumor antigen immunization. Taken together, our data showed that BAY 1905254 is a potential drug candidate for cancer immunotherapy, supporting its further evaluation.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Immunology Research Online (http://cancerimmunolres.aacrjournals.org/).

  • Cancer Immunol Res 2020;8:895–911

  • Received May 8, 2019.
  • Revision received November 15, 2019.
  • Accepted April 13, 2020.
  • Published first April 20, 2020.
  • ©2020 American Association for Cancer Research.
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Cancer Immunology Research: 8 (7)
July 2020
Volume 8, Issue 7
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Characterization of BAY 1905254, an Immune Checkpoint Inhibitor Targeting the Immunoglobulin-Like Domain Containing Receptor 2 (ILDR2)
Julia Huetter, Uwe Gritzan, Ilona Gutcher, Wolf-Dietrich Doecke, Merlin V. Luetke-Eversloh, Sven Golfier, Helge G. Roider, Anna-Lena Frisk, John Hunter, Andrew Pow, Andrew Drake, Zurit Levine, Ofer Levy, Meir Azulay, Inbal Barbiro, Gady Cojocaru, Ilan Vaknin, Bertolt Kreft and Lars Roese
Cancer Immunol Res July 1 2020 (8) (7) 895-911; DOI: 10.1158/2326-6066.CIR-19-0321

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Characterization of BAY 1905254, an Immune Checkpoint Inhibitor Targeting the Immunoglobulin-Like Domain Containing Receptor 2 (ILDR2)
Julia Huetter, Uwe Gritzan, Ilona Gutcher, Wolf-Dietrich Doecke, Merlin V. Luetke-Eversloh, Sven Golfier, Helge G. Roider, Anna-Lena Frisk, John Hunter, Andrew Pow, Andrew Drake, Zurit Levine, Ofer Levy, Meir Azulay, Inbal Barbiro, Gady Cojocaru, Ilan Vaknin, Bertolt Kreft and Lars Roese
Cancer Immunol Res July 1 2020 (8) (7) 895-911; DOI: 10.1158/2326-6066.CIR-19-0321
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