PT  - JOURNAL ARTICLE
AU  - Huetter, Julia
AU  - Gritzan, Uwe
AU  - Gutcher, Ilona
AU  - Doecke, Wolf-Dietrich
AU  - Luetke-Eversloh, Merlin V.
AU  - Golfier, Sven
AU  - Roider, Helge G.
AU  - Frisk, Anna-Lena
AU  - Hunter, John
AU  - Pow, Andrew
AU  - Drake, Andrew
AU  - Levine, Zurit
AU  - Levy, Ofer
AU  - Azulay, Meir
AU  - Barbiro, Inbal
AU  - Cojocaru, Gady
AU  - Vaknin, Ilan
AU  - Kreft, Bertolt
AU  - Roese, Lars
TI  - Characterization of BAY 1905254, an Immune Checkpoint Inhibitor Targeting the Immunoglobulin-Like Domain Containing Receptor 2 (ILDR2)
AID  - 10.1158/2326-6066.CIR-19-0321
DP  - 2020 Jul 01
TA  - Cancer Immunology Research
PG  - 895--911
VI  - 8
IP  - 7
4099  - http://cancerimmunolres.aacrjournals.org/content/8/7/895.short
4100  - http://cancerimmunolres.aacrjournals.org/content/8/7/895.full
SO  - Cancer Immunol Res2020 Jul 01; 8
AB  - 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.