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  3. Fidasimtamab

Fidasimtamab  (Synonyms: IBI-315; BH2950)

Cat. No.: HY-P99618 Purity: ≥95.0%
Technical Support

Fidasimtamab is a bispecific antibody targeting human epidermal growth factor receptor 2 (Her2) and programmed death protein 1 (PD-1), with a Ka of 3.55e-10 M for human Her2 and a Ka of 1.17e-9 M for human PD-1. Fidasimtamab cross-links Her2-positive tumor cells with PD-1-positive T cells to form immune synapses, blocks PD-1-ligand interactions, preserves antibody-dependent cellular cytotoxicity, induces gasdermin B (GSDMB)-mediated pyroptosis, and activates T cells. Fidasimtamab is applicable to relevant research on Her2-positive gastric cancer.

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

CAS No. : 2377419-89-9

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Description

Fidasimtamab is a bispecific antibody targeting human epidermal growth factor receptor 2 (Her2) and programmed death protein 1 (PD-1), with a Ka of 3.55e-10 M for human Her2 and a Ka of 1.17e-9 M for human PD-1. Fidasimtamab cross-links Her2-positive tumor cells with PD-1-positive T cells to form immune synapses, blocks PD-1-ligand interactions, preserves antibody-dependent cellular cytotoxicity, induces gasdermin B (GSDMB)-mediated pyroptosis, and activates T cells. Fidasimtamab is applicable to relevant research on Her2-positive gastric cancer[1].

Isotype

Human IgG1 kappa

Recommend Isotype Controls
Species Reactivity

Human

IC50 & Target

ERBB2 & PDCD1

In Vitro

Fidasimtamab binds to purified human PD-1 and Her2 proteins with high affinity, with KD values of 1.17 × 10-9 M and 3.55 × 10-10 M, respectively[1].
Fidasimtamab (600 nM; 30 min at 4 °C) induces a 24.10% association rate between N87 gastric cancer cells and activated human T cells[1].
Fidasimtamab (serial dilutions; 3 d) dose-dependently activates human CD4+ T cells in an MLR assay, inducing secretion of IFNγ and IL-2 with potency comparable to the parental anti-PD-1 antibody[1].
Fidasimtamab (600 nM; 24 h) significantly enhances T cell-mediated cytotoxicity against N87 and SNU-216 Her2-positive gastric cancer cells, as measured by increased LDH release[1].
Fidasimtamab (600 nM; 6 h) induces pyroptosis in N87 and SNU-216 Her2-positive gastric cancer cells in the presence of activated T cells, and increases IL-18 secretion by 24 h, via cleavage of GSDMB to its active N-terminal fragment[1].
Fidasimtamab (serial dilutions; 4 h at 37 °C) exhibits potent ADCC activity against N87 Her2-positive gastric cancer cells when incubated with human NK cells[1].
Fidasimtamab (600 nM; 24 h) induces a 2-3 fold increase in cell death in PDXO-1 Her2-positive gastric cancer organoids in the presence of T cells, and promotes association between T cells and organoids[1].
Conditioned media from Her2-positive gastric cancer cell-T cell cocultures treated with Fidasimtamab (600 nM; 24 h) activates human CD8+ T cells, increasing CD25 expression and enhancing IFNγ secretion[1].

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

Cell Cytotoxicity Assay[1]

Cell Line: N87 (Her2-positive gastric cancer) cells, SNU-216 (Her2-positive gastric cancer) cells, activated human T cells
Concentration: 600 nM
Incubation Time: 24 h
Result: Significantly increased LDH release from N87 and SNU-216 cells compared to control groups, indicating enhanced T cell-mediated tumor cell killing.

Cell Cytotoxicity Assay[1]

Cell Line: N87 (Her2-positive gastric cancer) cells, human NK cells
Concentration: Serial dilutions
Incubation Time: 4 h at 37 °C
Result: Demonstrated potent ADCC activity against N87 cells, with stronger tumor-killing activity than its parental trastuzumab.
In Vivo

Fidasimtamab (IBI-315/BH2950) (5 mg/kg; i.p.; every 3 days; 2 weeks) achieves a 116.8% tumor inhibition rate in human PBMC-reconstituted NOG mice bearing N87 Her2-positive gastric cancer, with enhanced intratumoral T cell infiltration[1].
Fidasimtamab (IBI-315/BH2950) (5 mg/kg; i.p.; every 3 days; 2 weeks) achieves a 77% tumor volume reduction in human PBMC-reconstituted NOG mice bearing PDX-1 Her2-positive gastric cancer, with enhanced intratumoral T cell infiltration, activation, and proliferation[1].
Fidasimtamab (IBI-315/BH2950) (5 mg/kg; i.p.; every 3 days; 2 weeks) loses its significant tumor inhibitory activity in human PBMC-reconstituted NOG mice bearing GSDMB-knockdown N87 Her2-positive gastric cancer, confirming dependency on GSDMB-mediated pyroptosis[1].

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

Animal Model: NOG (NOD/ShiLtj-scid IL2rg) (female, 4 weeks old, subcutaneously implanted with N87 human Her2-positive gastric cancer cells, reconstituted with human PBMCs)[1]
Dosage: 5 mg/kg
Administration: i.p.; every 3 days; 2 weeks
Result: Achieved a tumor volume of 54.1 mm3 (day 31), corresponding to a 116.8% tumor inhibition rate relative to control.
Induced the highest infiltration of CD3+, CD8+, and CD4+ lymphocytes in N87 tumors compared to control, parental antibodies, and parental antibody combination groups.
Animal Model: NOG (NOD/ShiLtj-scid IL2rg) (female, 4 weeks old, subcutaneously implanted with PDX-1 human Her2-positive gastric cancer tissue, reconstituted with human PBMCs)[1]
Dosage: 5 mg/kg
Administration: i.p.; every 3 days; 2 weeks
Result: Achieved a tumor volume of 182.2 mm3 (day 39), corresponding to a 77% reduction relative to control.
Induced the highest infiltration of CD3+, CD8+, and CD4+ lymphocytes in PDX-1 tumors compared to control, parental antibodies, and parental antibody combination groups.
Increased the proportion of granzyme A-positive CD8+ T cells in PDX-1 tumors relative to control.
Boosted the frequency of Ki67+ proliferating CD8+ and CD4+ T cells, CD107a+ activated CD8+ and CD4+ T cells, CD25+ activated CD8+ and CD4+ T cells, and Tbet+IFNγ+ CD3+ T cells in PDX-1 tumors relative to control.
Animal Model: NOG (NOD/ShiLtj-scid IL2rg) (female, 4 weeks old, subcutaneously implanted with GSDMB-knockdown N87 human Her2-positive gastric cancer cells, reconstituted with human PBMCs)[1]
Dosage: 5 mg/kg
Administration: i.p.; every 3 days; 2 weeks
Result: Showed almost completely blocked tumor inhibitory effect in GSDMB-knockdown N87 tumors, with no significant reduction in tumor volume relative to control.
Reduced infiltration of CD3+ and CD8+ T cells in GSDMB-knockdown N87 tumors compared to its effect in wild-type N87 tumors.
Gene ID

2064  [NCBI] & 5133  [NCBI]

Accession
Application

ELISA, FACS, Functional assay

Conjugated

Unconjugated

Reconsititution

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

Molecular Weight

144.62 kDa

CAS No.
Appearance

Liquid

Color

Colorless to light yellow

SMILES

[Fidasimtamab]

Shipping

Shipping with dry ice.

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.

Format
  • Human IgG1 kappa
Purity & Documentation

Purity: ≥95.0%

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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Fidasimtamab
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