PF-07260437
PF-07260437 is a bispecific monoclonal antibody targeting B7-H4 and CD3, with Kd values of 63.5 nM and 66.75 nM against human and cynomolgus monkey CD3, respectively. PF-07260437 simultaneously binds B7-H4 on tumor cells and the CD3ε subunit in the T cell receptor complex, forming a tumor cell-bispecific antibody-T cell trimer. This process establishes an immune synapse and initiates non-MHC-dependent T cell activation, proliferation, and release of cytotoxic molecules such as granzyme B to kill tumor cells. PF-07260437 can be used in research related to advanced or metastatic breast cancer, ovarian cancer, and endometrial cancer.
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Biologische Aktivität
Beschreibung
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| MX1 | EC50 |
0.062 nM
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Significantly inhibits tumor cell proliferation.
Significantly inhibits tumor cell proliferation.
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40366350 |
| MDA-MB-468 | EC50 |
0.512 nM
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Significantly inhibits tumor cell proliferation.
Significantly inhibits tumor cell proliferation.
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40366350 |
| HCC1954 | EC50 |
0.797 nM
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Significantly inhibits tumor cell proliferation.
Significantly inhibits tumor cell proliferation.
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40366350 |
| T47D | EC50 |
0.762 nM
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Significantly inhibits tumor cell proliferation.
Significantly inhibits tumor cell proliferation.
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40366350 |
| MDA-MB-453 | EC50 |
15.206 nM
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Significantly inhibits tumor cell proliferation.
Significantly inhibits tumor cell proliferation.
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40366350 |
In Vitro
PF-07260437 (0.1 μM-1 mM; 2 h) exhibits dose-dependent targeted binding activity in MX-1, HEK-293-hB7-H4 cells, and primary human/cynomolgus monkey T cells, with an affinity of 63.5 nM for human CD3 and 66.75 nM for cynomolgus monkey CD3[1].
PF-07260437 (0.1 μM-1 mM) exerts T cell-mediated cytotoxicity in MX-1, MDA-MB-468, MDA-MB-453, HCC-1954 and T-47D cells co-cultured with T cells at an E:T ratio of 2.5:1, and its EC50 value is negatively correlated with B7-H4 receptor density (R2 = 0.8045)[1].
PF-07260437 (1 μM-1 mM; 2-6 days) exerts no direct inhibitory effect on tumor cell proliferation in T-47D, HCC-1954 and MX-1 cells in the absence of T cells[1].
PF-07260437 induces activated T cells co-cultured with B7-H4-expressing breast cancer cells to release IFN-γ, IL-10, IL-2, and TNF-α in a B7-H4-dependent manner[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
PF-07260437 (1.5 ng/kg-0.5 mg/kg; i.v.; once weekly for three doses; approximately 25 days) dose-dependently and significantly inhibits tumor growth in orthotopic mammary fat pad xenograft NSG mouse models implanted with HCC-1954[1].
PF-07260437 (0.5 mg/kg; i.v.; once weekly, administered on days 7 and 14; observation for 35 days) induces complete tumor regression in an adoptively transferred T-47D (HR+HER2-) subcutaneous xenograft NSG mouse model[1].
PF-07260437 (1.5 ng/kg-0.5 mg/kg; i.v. or s.c.; once weekly for 3 doses; 35 days) induces complete tumor regression in an adoptively transferred MX-1-Luc subcutaneous xenograft NSG mouse model[1].
PF-07260437 (0.01-0.5 mg/kg; i.v. or s.c.; once weekly for 3 doses; within 25 days) dose-dependently inhibits tumor growth in NSG mouse models implanted with a variety of breast cancer PDXs (e.g., PDX-BRX-11380, PDX-BRX-24301, PDX-BRX-26305)[1].
PF-07260437 (0.5 mg/kg; s.c.; once weekly; 60 days) exhibits synergistic tumor-shrinking activity when combined with Fulvestrant (HY-13636) and Palbociclib (HY-50767) in a mouse model of adoptive transfer ZR-75-1 xenografts[1].
PF-07260437 (0.5 mg/kg; s.c.; single dose; 60 days), in combination with anti-PD-1 treatment, exhibits synergistic activity in enhancing anti-tumor effects and increasing T-cell infiltration in a humanized CD3ε-transgenic, immunocompetent mouse model orthotopically implanted with human B7-H4-expressing E0771 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Immunodeficient NSG female mice were subcutaneously inoculated with the human triple-negative breast cancer (TNBC) cell line MDA-MB-468, and received an intravenous injection of untreated human PBMCs 6 days prior to treatment initiation to establish an immune-reconstituted model[1]
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Dosage:0.02, 0.04, 0.1, 0.5, 3 mg/kg
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Administration:i.v.; once weekly on days (3 doses total); treated and monitored up to approximately day 25.
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Result:Exhibited significant dose-dependent anti-tumor activity, achieving 133% tumor growth inhibition (TGI) at doses as low as 0.04 mg/kg.
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Animal Model:NSG female mice were orthotopically inoculated in the mammary fat pad with the human HER2+ breast cancer cell line HCC-1954, and received an intravenous injection of human PBMCs 6 days prior to treatment initiation.[1]
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Dosage:0.0015, 0.005, 0.05, 0.5 mg/kg
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Administration:i.v.; once weekly on days (3 doses total); treated and monitored up to approximately day 25.
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Result:Induced significant and dose-dependent tumor growth inhibition.
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Animal Model:NSG mice, supplemented with a 90-day release estradiol pellet, were subcutaneously inoculated with the human HR+HER2- breast cancer cell line T-47D, and received an intravenous injection of adoptively transferred in vitro expanded human T cells 24 hours after the first dose[1]
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Dosage:0.5 mg/kg
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Administration:i.v.; once weekly on days (3 doses total); treated and monitored up to day 35
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Result:Induced complete tumor regression in all mice with no tumor regrowth observed by day 35.
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Animal Model:NSG mice were subcutaneously inoculated with the luciferase-expressing human TNBC cell line MX-1-Luc, and received an intravenous injection of adoptively transferred in vitro expanded human T cells 24 hours after the first dose[1]
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Dosage:0.0015 (i.v.), 0.01, 0.05, 0.5 mg/kg (IV and s.c.)
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Administration:i.v. or s.c.; once weekly (3 doses total); treated and monitored up to day 35
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Result:Led to complete tumor regression at 0.05 mg/kg and 0.5 mg/kg doses (via both IV and SC routes), and sustained anti-tumor activity with no tumors growing back by day 35.
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Animal Model:NSG mice were subcutaneously implanted in the flank with patient-derived breast cancer tissue fragments (PDX-BRX-11380, PDX-BRX-24301, PDX-BRX-26305), and received an intravenous injection of human PBMCs 6 days prior to treatment initiation.[1]
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Dosage:0.01, 0.07, 0.5 mg/kg
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Administration:i.v. or s.c.; once weekly (3 doses total); treated and monitored up to day 20-25
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Result:Induced dose-dependent tumor growth inhibition, achieving over 100% tumor growth inhibition (TGI) at the 0.5 mg/kg dose.
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Animal Model:Estradiol-supplemented NSG mice were subcutaneously inoculated with the human HR+ breast cancer cell line ZR-75-1[1]
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Dosage:0.5 mg/kg (combined with Fulvestrant 10 mg/kg and Palbociclib 10 mg/kg)
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Administration:s.c.; once weekly (Fulvestrant and Palbociclib schedules were maintained); treated and monitored up to day 60.
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Result:Induced synergistic tumor shrinkage and regression effects, and upregulated immune checkpoint genes (PD-L1, PD-1, etc.) in the tumor microenvironment when combined with standard-of-care therapies (fulvestrant and palbociclib).
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Animal Model:Immunocompetent mice, genetically engineered to express the human CD3ε transgene, were orthotopically inoculated in the mammary fat pad with the murine breast cancer cell line E0771-hB7-H4 stably expressing human B7-H4[1]
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Dosage:0.5 mg/kg (combined with a surrogate murine anti-PD-1 antibody 10 mg/kg)
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Administration:s.c.; single dose; anti-PD-1 antibody was i.p. every 3 days for 6 doses; treated and monitored up to day 60.
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Result:Significantly enhanced synergistic anti-tumor activity (106% TGI) and led to a substantial increase in intratumoral CD3 and CD8 T-cell infiltration 9 days post-treatment when combined with an anti-PD-1 antibody.
Chemical Information
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Reinheit & Dokumentation
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Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
PF-07260437 Related Classifications
HY-P992524 Related Classifications
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