2. Immunology/Inflammation Apoptosis
  3. CD38 Fc Receptor (FcR) Apoptosis
  4. 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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SAR442085

SAR442085 Chemical Structure

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Description

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[1][2][3][4].

Species Reactivity

Human
In Vitro

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 Related Antibodies
In Vivo

SAR442085 (1.25-10 mg/kg) exhibits potent single-agent in vivo activity in a humanized multiple myeloma mouse model[1].
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.

Animal Model: Human Fc receptor transgenic C57BL/6 (male and female, injected intravenously with 5×105 EL4-huCD38 cells at day 0)[2]
Dosage: 10 mg/kg; 1.25 mg/kg
Administration: i.p.; on days 1, 4, 7, 11, 14
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.
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]
Dosage: 10 mg/kg
Administration: i.p.; 6 injections every 2-3 days; starting at day 7 post-tumor injection
Result: Significantly reduced serum M-spike levels compared with isotype control, daratumumab, and isatuximab.
Induced better disease-free survival than daratumumab and isatuximab.
Gene ID

952  [NCBI]

Accession
Target

CD38
Application

ELISA, FACS, Functional assay
Conjugated

Unconjugated
Reconsititution

The product can be reconstituted/diluted with sterile PBS or saline.
Formulation

Please refer to the lot-specific COA for specific buffer information.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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SAR442085 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

SAR442085SAR 442085SAR-442085CD38Fc Receptor (FcR)ApoptosisFc ReceptorFcγRIIIaFcγRIIaHEK293TRPMI-8226KMS-12-BMNK cellmultiple myelomarelapsed/refractory multiple myelomaMOLP-8Inhibitorinhibitorinhibit

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