On November 12, 2021 OncoResponse, a clinical-stage biotech company advancing immunotherapies derived from the immune systems of elite cancer responders, reported the presentation of data on multiple immuno-oncology programs at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 36th Annual Meeting (Press release, OncoResponse, NOV 12, 2021, View Source [SID1234595489]).
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Data presented included preclinical findings on three monoclonal antibodies developed utilizing OncoResponse’s proprietary B-cell platform that leverages data from elite responders to cancer immunotherapy in order to rapidly identify fully human therapeutic antibodies.
"OncoResponse is focused on the development of human antibodies that modulate immune cell activity and enhance immunotherapy responses. Our data presented at SITC (Free SITC Whitepaper) highlight three investigational targets that provide initial and compelling data demonstrating immune activity and the ability to modulate the tumor microenvironment," said Kamal Puri, PhD, Chief Scientific Officer of OncoResponse.
Clifford Stocks, OncoResponse Chief Executive Officer, added, "We look forward to the continued evaluation of our lead candidate, OR2805, in an ongoing clinical trial as well as further advancing additional targets toward IND-enabling studies."
Presentation highlights include:
Poster: 271
Development of OR2805, an anti-CD163 antibody derived from an elite responder to checkpoint inhibitor therapy that relieves immunosuppression caused by M2c macrophages
The evaluation of OR2805 alone and in combination with an anti-PD1 or -PD-L1 antibody in various preclinical in vitro and in vivo assays modeling an immunosuppressive tumor microenvironment, demonstrated:
OR2805 binds with high specificity to M2 macrophages and tumor-associated macrophages (TAMs) in human primary non-small cell lung cancer tumors
OR2805 reduces expression of cell-surface markers associated with tumor-promoting M2c macrophages and relieves the immunosuppressive effect on T-cell activation and proliferation in coculture assays
Robust anti-tumor activity was demonstrated in lung cancer xenograft models in humanized NSG-SGM3 mice. Additionally,
OR2805 reduces TAM mediated immunosuppression and enhances anti-tumor immune responses.
Combination with OR2805 restores and amplifies anti-PD-1 and anti-PD-L1 activity in coculture assays
OR2805 toxicology predicts a tolerable safety profile
OR2805 is currently being evaluated in a Phase 1/2 study in patients with advanced cancer
Poster: 262
Preclinical characterization of humanized anti-Siglec-15 antibodies that rescue T cells from macrophage-mediated immune suppression
The identification of novel humanized anti-Siglec-15 antibodies identified using functional screens modeling Siglec-15-mediated immune suppression by M2c macrophages demonstrated:
Ability of antibodies to block the interaction of Siglec-15 with an immune suppressive checkpoint on T cells and restore T-cell effector function.
Rescue of T cell activation and proliferation from M2c macrophage-mediated immunosuppression in M2c/CD8 coculture assays.
Restoration of effector function of activated and exhausted T cells from M2c-mediated immune suppression, with favorable half-life and anti-tumor activity in humanized mouse models.
Data provide a rationale for further development of these antibodies as anti-cancer immunotherapy.
Poster: 276
Discovery and preclinical characterization of anti-LILRB2 antibodies that rescue T cells from macrophage-mediated immune suppression
Identification of anti-LILRB2 antibodies that demonstrate:
Enhanced IFN-γ production by peripheral blood mononuclear cells and TNF-α secretion by macrophages
Relief of CD8+ T cells from M2c macrophage-mediated immunosuppression
Anti-tumor activity in an SK-MEL-5 tumor model in humanized NSG-SGM3 mice with up to 79% tumor growth inhibition and 44% tumor regression
Results support further development of lead anti-LILRB2 antibodies for cancer immunotherapy
Accessing Posters
The OncoResponse posters presented at SITC (Free SITC Whitepaper) are accessible from the Publications & Presentations page of OncoResponse website at View Source
About OR2805
OR2805 is a fully human antibody discovered using B cells derived from an elite responder to checkpoint inhibitor (CPI) therapy. This antibody binds to CD163 which is highly expressed on tumor associated macrophages (TAMs) that create an immunosuppressive tumor microenvironment and inhibit anti-tumor T-cell responses. High frequency of CD163-expressing TAMs generally predicts an unfavorable prognosis in solid tumors. OR2805 is designed to improve anti-tumor T-cell responses, by reversing the immunosuppression of TAMs, as a therapeutic strategy for monotherapy and in combination with CPI.