1. Immunology/Inflammation
  2. Glycoprotein VI Interleukin Related
  3. SAR444200

SAR444200 is a nanobody T-cell engager targeting GPC3 (glypican-3) and TCRαβ (T-cell receptor αβ). SAR444200 has a KD of 0.023 nM for human GPC3 and a KD of 5.2 nM for human TCRαβ. SAR444200 mediates T-cell-dependent cytotoxicity, with high selectivity and killing activity against GPC3-positive tumor cells. SAR444200 binds to GPC3 in a dual-epitope manner, and binds to TCRαβ via its N-terminal nanobody, forming an artificial immunological synapse between T cells and tumor cells. SAR444200 can be used for the research of GPC3+ solid tumors, including liver cancer, lung squamous cell carcinoma and melanoma.

For research use only. We do not sell to patients.

SAR444200

SAR444200 Chemical Structure

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Description

SAR444200 is a nanobody T-cell engager targeting GPC3 (glypican-3) and TCRαβ (T-cell receptor αβ). SAR444200 has a KD of 0.023 nM for human GPC3 and a KD of 5.2 nM for human TCRαβ. SAR444200 mediates T-cell-dependent cytotoxicity, with high selectivity and killing activity against GPC3-positive tumor cells. SAR444200 binds to GPC3 in a dual-epitope manner, and binds to TCRαβ via its N-terminal nanobody, forming an artificial immunological synapse between T cells and tumor cells. SAR444200 can be used for the research of GPC3+ solid tumors, including liver cancer, lung squamous cell carcinoma and melanoma[1][2].

Species Reactivity

Human

IC50 & Target[1]

IL-6

 

IL-2

 

In Vitro

SAR444200 binds to human and cynomolgus monkey TCRαβ with single-digit nanomolar affinity, human and cynomolgus monkey GPC3 with sub-nanomolar affinity, and human and cynomolgus monkey albumin with single-digit nanomolar affinity, with lower affinity to mouse orthologues and no cross-reactivity to mouse TCR[1].
SAR444200 (24 h) binds to membrane-bound human GPC3 with sub-nanomolar affinity and membrane-bound cynomolgus monkey GPC3 with low sub-nanomolar affinity[1].
SAR444200 (60 h) potently induces T-cell-dependent cellular cytotoxicity of GPC3+ human HepG2, NCI-H661, and HuH-7 cells with sub-nanomolar EC50 values, shows cross-reactive cytotoxicity against cynomolgus monkey GPC3-expressing HEK293 cells, and exhibits no activity against GPC3-low NCI-H23 cells[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

SAR444200 (0.2-2.0 mg/kg; intravenous injection; once every 3 days; 5 doses total) induces tumor regression in HepG2 hepatocellular carcinoma humanized NOG mice and HuH-7 hepatocellular carcinoma humanized NOG mice[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: NOG (NOD.Cg-PrkdcscidIL2tm1Sug/Jital) (10-week-old female, humanized with HepG2 cells and human T cells)[1]
Dosage: 2.0 mg/kg; 0.7 mg/kg; 0.2 mg/kg
Administration: i.v.; every third day; 5 doses
Result: Showed significant antitumor activity with 100% tumor inhibition at day 33, and induced 1 complete regression and 5 partial regressions at 2.0 mg/kg.
Showed significant antitumor activity with 100% tumor inhibition at day 33, and induced 1 complete regression and 3 partial regressions at 0.7 mg/kg.
Showed non‑significant antitumor activity with 29% tumor inhibition at day 33 at 0.2 mg/kg.
Animal Model: NOG (NOD.Cg-PrkdcscidIL2tm1Sug/Jital) (10-week-old female, humanized with HuH-7 cells and human T cells)[1]
Dosage: 2.0 mg/kg; 0.7 mg/kg; 0.2 mg/kg
Administration: i.v.; every third day; 5 doses
Result: Achieved significant antitumor activity with 100% tumor inhibition at day 35 and induced 3 complete regressions and 1 partial regression at 0.7 mg/kg.
Displayed significant antitumor activity with 67% tumor inhibition at day 35 and induced 1 complete regression and 3 partial regressions at 2.0 mg/kg.
Showed non-significant antitumor activity with 54% tumor inhibition at day 35 at 0.2 mg/kg.
Gene ID

2719  [NCBI]

Accession
Target

TCRαβ & GPC3

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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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.

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Product Name:
SAR444200
Cat. No.:
HY-P992457
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