SAR442085
SAR442085 is an Fc-engineered anti-CD38 monoclonal antibody with a Kd of 0.2 nM for human CD38. SAR442085 inhibits CD38, induces apoptosis, and triggers antibody-dependent cellular cytotoxicity and phagocytosis in CD38-expressing tumor cells. SAR442085 binds allelic variants of FcγRIIa and FcγRIIIa, enhances NK cell activation, degranulation and cytokine secretion, and exerts anti-tumor activity in human Fc receptor transgenic mice. SAR442085 can be used in the research of multiple myeloma.
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Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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Chemical Information
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Actividad biológica
Human
SAR442085 potently induces ADCC against RPMI-8226 multiple myeloma cells with an EC50 more than 8-fold lower than Daratumumab (HY-P9915)[1].
SAR442085 inhibits CD38 enzymatic activity[1].
SAR442085 exhibits potent antibody-dependent cellular cytotoxicity (ADCC) and NK cell activation activity against primary myeloma cells and low CD38-density myeloma cells, and enhances CD16 binding to promote natural killer (NK) cell activation and degranulation, thereby killing primary multiple myeloma plasma cells in patient bone marrow aspirates[1][3].
SAR442085 induces potent direct pro-apoptotic activity in SU-DHL-8 lymphoma cells and directly triggers apoptosis in CD38-expressing multiple myeloma cells in vitro[1][2].
SAR442085 (0-100 nM) binds to purified recombinant human CD38 with a Kd of 0.2 nM, demonstrating high affinity for its target antigen[2].
SAR442085 (0-5 μM) binds to purified human FcγRIIIa-158F with a Kp of 119 nM and to FcγRIIIa-158V with a Kp of 46 nM[2].
SAR442085 binds to purified human FcγRIIa-131H with a KD of 720 nM and to FcγRIIa-131R with a KD of 2150 nM, demonstrating specific binding to both activating FcγRIIa variants[2].
SAR442085 (30 minutes at 4°C) binds to CD38+ MOLP-8 MM cells with an apparent Kd of 1.1 nM, showing high target binding affinity[2].
SAR442085 (30 minutes at 4°C) binds with significantly higher apparent affinity and maximal binding to HEK293T cells overexpressing FcγRIIIa-158F, FcγRIIIa-158V, FcγRIIa-131R, or FcγRIIa-131H than Daratumumab (HY-P9915) and Isatuximab (HY-P9976)[2].
SAR442085 (dose range; 30 minutes pre-incubation, 1 hour coculture) induces significantly more potent ADCC against RPMI-8226, MOLP-8, and KMS-12-BM MM cells via NK-92.FcγRIIIa-158F and NK-92.FcγRIIIa-158V effector cells[2].
SAR442085 (dose range; 30 minutes pre-incubation, overnight coculture) induces significantly more potent and efficacious ADCC against RPMI-8226 and KMS-12-BM MM cells via HD PBMC effector cells[2].
SAR442085 (dose range; 30 minutes pre-incubation, overnight coculture) induces significantly more potent ADCC against RPMI-8226 MM cells via purified HD NK effector cells[2].
SAR442085 (dose range; 15 minutes pre-incubation, overnight coculture) induces significantly more potent and efficacious ADCP against RPMI-8226 MM cells via HD monocyte-derived macrophages[2].
SAR442085 (1 hour) inhibits CD38 ecto-enzymatic activity in RPMI-8226 MM cells to a similar extent as Isatuximab (HY-P9976) and significantly more than Daratumumab (HY-P9915)[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
SAR442085 (1.25-10 mg/kg; i.p.; on days 1, 4, 7, 11, 14) provides 90% long-term survival in EL4-huCD38-bearing huFcγR mice at 10 mg/kg, and maintains significant survival benefits at 1.25 mg/kg, outperforming Daratumumab (HY-P9915) and Isatuximab (HY-P9976)[2].
SAR442085 (10 mg/kg; i.p.; 6 injections every 2-3 days; starting at day 7 post-tumor injection) reduces multiple myeloma burden (lower M-spike levels) and improves disease-free survival more effectively than Daratumumab (HY-P9915) and Isatuximab (HY-P9976) in an NK cell-dependent VK*MYC myeloma mouse model[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Human Fc receptor transgenic C57BL/6 (male and female, injected intravenously with 5×105 EL4-huCD38 cells at day 0)[2]
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Dosage:10 mg/kg; 1.25 mg/kg
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Administration:i.p.; on days 1, 4, 7, 11, 14
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Result:Achieved 90% long-term survival (up to 90 days post-tumor implantation) at 10 mg/kg, compared with 50% survival for daratumumab- and isatuximab-treated mice.
Maintained significant survival benefits at 1.25 mg/kg, while daratumumab and isatuximab showed no survival improvement compared with isotype control.
Increased the percentage of splenic NK cells, macrophages, and dendritic cells compared with isotype, isatuximab, or daratumumab treatment.
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Animal Model:Rag2-/-Il2rg-/- (male and female, sex-matched with NK cell donors, reconstituted with NK cells from human Fc receptor transgenic C57BL/6 mice, injected intravenously with Vk12653-huCD38 cells 1 week post-NK cell reconstitution)[2]
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Dosage:10 mg/kg
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Administration:i.p.; 6 injections every 2-3 days; starting at day 7 post-tumor injection
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Result:Significantly reduced serum M-spike levels compared with isotype control, daratumumab, and isatuximab.
Induced better disease-free survival than daratumumab and isatuximab.
CD38
Unconjugated
The product can be reconstituted/diluted with sterile PBS or saline.
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Product Image
ELISA, FACS, Functional assay
Chemical Information
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Formulation
Please refer to the lot-specific COA for specific buffer information.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
[2]. Kassem S, et al. SAR442085, a novel anti-CD38 antibody with enhanced antitumor activity against multiple myeloma. Blood. 2022;139(8):1160-1176. [Content Brief]
[3]. Kapoor P, et al. An open-label, first-in-human, single agent, dose escalation study for the evaluation of safety and efficacy of SAR442085 in patients with relapsed or refractory multiple myeloma. Eur J Haematol. 2024;113(5):593-605. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
SAR442085 Related Classifications
HY-P992455 Related Classifications
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