291 Dual-specific antibodies blocking both PD-L1 and PD-L2 engagement of PD-1 restore anti-tumor immunity

نویسندگان

چکیده

Background Inhibition of T cell activation and effector function via engagement the co-inhibitory receptor PD-1 is a critical mechanism enabling tumors to evade host immunity. The two ligands for PD-1, PD-L1 PD-L2, can be expressed by variety immunosuppressive stromal cells, particularly myeloid lineage, endothelial themselves. In addition engages B7-1 in an additional interaction. Blocking only or thus does not relieve all inhibitory components this pathway. We hypothesized that bispecific antibodies blocking both PD-L2 could more fully restore tumor-specific potentiate anti-cancer immunotherapy. Furthermore, we speculated enhancing cytotoxic these might further enhance their efficacy through depletion tumor cells supportive stroma. Methods investigated capacity monoclonal capable bivalent binding PD-1-suppressed vitro. To assess vivo therapeutic efficiency PD-Ligand with ADCC capacities, mouse IgG2a modified human IgG1 versions were generated. assessed activity vitro using bioluminescent reporter assay, syngeneic human-cell derived tumors. Results generated equivalent FDA approved antibody Pembrolizumab. Moreover, our lead significantly higher FcγRIIa than FDA-approved clinical vivo, ADCC-capable suppress growth U2940 lymphoma immunodeficient mice efficiently Rituximab, model PD-L1/PD-L2 double positive colon carcinoma, demonstrate superiority limit increase survival. treatment increases proliferation cytotoxicity reduces density stroma vivo. Conclusions display potential existing anti-PD-1 represent new class pathway therapeutics significant cancers. Acknowledgements I would like thank Anupallavi Srinivasamani, PhD student Michael Curran’s lab, who performed considerable amount work on project before joined.

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ژورنال

عنوان ژورنال: Journal for ImmunoTherapy of Cancer

سال: 2021

ISSN: ['2051-1426']

DOI: https://doi.org/10.1136/jitc-2021-sitc2021.291