STI-6643 is a fully human IgG4 antibody that targets CD47. STI-6643 blocks CD47 - SIRPα interaction, and enables macrophage-mediated phagocytosis of tumor cells. STI-6643 shows anti-tumor activity in mouse lymphoma xenograft models. STI-6643 can be used for the research of Burkitt's lymphoma, solid tumors, relapsed or refractory tumors, and lymphoma. The isotype control for STI-6643 can refer to Human IgG4 (S228P) kappa, Isotype Control [1] [2].
In Vivo, STI-6643 (0.1-60 mg/kg; i.v.; 3x/week; 2 consecutive weeks) exhibits potent dose-dependent anti-tumor activity and survival benefits in a mouse disseminated Burkitt's lymphoma xenograft model[1]. STI-6643 (20 mg/kg; i.v.; 3x/week; 2 consecutive weeks) in combination with Rituximab enhances anti-tumor activity and survival in a mouse disseminated Burkitt's lymphoma xenograft model[1]. STI-6643 (10 mg/kg; s.c.; 6 doses on days 6, 8, 10, 13, 15 and 17) preserves functional human T cells in a mouse xenograft GVHD model[1].
In Vitro, STI-6643 binds to human CD47 with a Kd of 76 nM, with lower affinity for cynomolgus (177 nM) and canine (134 nM) CD47 antigens[1]. STI-6643 (25 min) binds dose-dependently to human MDA-MB-231 (EC50 ~30.0 µg/mL), human RAJI (EC50 6.64 µg/mL), canine OSCA-40 (EC50 ~30.0 µg/mL), and canine OSCA-78 (EC50 ~30.0 µg/mL) cancer cells[1]. STI-6643 (0.09-200 µg/mL; 15 min) dose-dependently blocks the CD47/SIRPα interaction on human CCRF-CEM cells with an IC50 of 3.65 µg/mL, without reaching saturation at concentrations up to 200 µg/mL[1]. STI-6643 (0.0001-10 µg/mL; 30 min) enhances macrophage-mediated phagocytosis of human RAJI-GFP cells[1]. STI-6643 (1.5625-50 µg/mL) does not exhibit direct tumor cell killing activity on human CCRF-CEM leukemia cells[1]. STI-6643 (100 µg/mL; 25 min) exhibits negligible binding to human (EC50 = 11.76 µg/mL) and cynomolgus monkey (EC50 = 20.32 µg/mL) RBCs, with slightly stronger binding to canine RBCs (EC50 = 5.10 µg/mL)[1]. STI-6643 (0.001-300 µg/mL; 20 h) does not induce hemagglutination of human or cynomolgus monkey RBCs at concentrations up to 300 µg/mL, and exhibits weak, 100-fold less potent hemagglutination activity than Hu5F9 in canine RBCs[1]. STI-6643 (0.001-100 µg/mL; 3 days) preserves human T cell survival and functionality in a superantigen stimulation assay, with minimal impact on IFN-γ secretion[1]. STI-6643 (0.001-500 µg/mL; 6 days) preserves the survival of human CD4+, CD8+, CD19+, and CD56+ immune cells[1]. STI-6643 (2.5-5 ng/mL; 30 min) in combination with Rituximab enhances macrophage-mediated phagocytosis of human RAJI-GFP cells[1].
References:
[1]. Thaker YR, et al. A Novel Affinity Engineered Anti-CD47 Antibody With Improved Therapeutic Index That Preserves Erythrocytes and Normal Immune Cells. Front Oncol. 2022;12:884196. Published 2022 May 19.
[2]. Xu S, et al. Targeting immune checkpoints on tumor-associated macrophages in tumor immunotherapy. Front Immunol. 2023 May 29;14:1199631.
In Vivo, STI-6643 (0.1-60 mg/kg; i.v.; 3x/week; 2 consecutive weeks) exhibits potent dose-dependent anti-tumor activity and survival benefits in a mouse disseminated Burkitt's lymphoma xenograft model[1]. STI-6643 (20 mg/kg; i.v.; 3x/week; 2 consecutive weeks) in combination with Rituximab enhances anti-tumor activity and survival in a mouse disseminated Burkitt's lymphoma xenograft model[1]. STI-6643 (10 mg/kg; s.c.; 6 doses on days 6, 8, 10, 13, 15 and 17) preserves functional human T cells in a mouse xenograft GVHD model[1].
In Vitro, STI-6643 binds to human CD47 with a Kd of 76 nM, with lower affinity for cynomolgus (177 nM) and canine (134 nM) CD47 antigens[1]. STI-6643 (25 min) binds dose-dependently to human MDA-MB-231 (EC50 ~30.0 µg/mL), human RAJI (EC50 6.64 µg/mL), canine OSCA-40 (EC50 ~30.0 µg/mL), and canine OSCA-78 (EC50 ~30.0 µg/mL) cancer cells[1]. STI-6643 (0.09-200 µg/mL; 15 min) dose-dependently blocks the CD47/SIRPα interaction on human CCRF-CEM cells with an IC50 of 3.65 µg/mL, without reaching saturation at concentrations up to 200 µg/mL[1]. STI-6643 (0.0001-10 µg/mL; 30 min) enhances macrophage-mediated phagocytosis of human RAJI-GFP cells[1]. STI-6643 (1.5625-50 µg/mL) does not exhibit direct tumor cell killing activity on human CCRF-CEM leukemia cells[1]. STI-6643 (100 µg/mL; 25 min) exhibits negligible binding to human (EC50 = 11.76 µg/mL) and cynomolgus monkey (EC50 = 20.32 µg/mL) RBCs, with slightly stronger binding to canine RBCs (EC50 = 5.10 µg/mL)[1]. STI-6643 (0.001-300 µg/mL; 20 h) does not induce hemagglutination of human or cynomolgus monkey RBCs at concentrations up to 300 µg/mL, and exhibits weak, 100-fold less potent hemagglutination activity than Hu5F9 in canine RBCs[1]. STI-6643 (0.001-100 µg/mL; 3 days) preserves human T cell survival and functionality in a superantigen stimulation assay, with minimal impact on IFN-γ secretion[1]. STI-6643 (0.001-500 µg/mL; 6 days) preserves the survival of human CD4+, CD8+, CD19+, and CD56+ immune cells[1]. STI-6643 (2.5-5 ng/mL; 30 min) in combination with Rituximab enhances macrophage-mediated phagocytosis of human RAJI-GFP cells[1].
References:
[1]. Thaker YR, et al. A Novel Affinity Engineered Anti-CD47 Antibody With Improved Therapeutic Index That Preserves Erythrocytes and Normal Immune Cells. Front Oncol. 2022;12:884196. Published 2022 May 19.
[2]. Xu S, et al. Targeting immune checkpoints on tumor-associated macrophages in tumor immunotherapy. Front Immunol. 2023 May 29;14:1199631.