ZL-1211
ZL-1211 is an anti-CLDN18.2 monoclonal antibody. ZL-1211 exhibits enhanced binding affinity to CD16A. ZL-1211 induces ADCC-mediated cell lysis and triggers the production of IFNγ, TNFα and IL6. ZL-1211 promotes antibody-dependent cellular cytotoxicity. ZL-1211 exerts anti-tumor activity in a mouse xenograft model of gastric cancer. ZL-1211 can be used for the research of gastric cancer.
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Activité biologique
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Activité biologique
Human IgG1 kappa
Human
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IL-6 |
ZL-1211 (1 h) specifically binds to CLDN18.2 on the surface of CHO cells and NUGC4 cells with overexpressed CLDN18.2[1].
ZL-1211 (serial dilution concentrations; 4-5 h) potently induces ADCC against CLDN18.2-overexpressing NUGC4-hCLDN18.2 cells via PBMC effector cells[1].
ZL-1211 (at serially diluted concentrations) potently induces ADCC effects against MIA-PaCa2-hCLDN18.2 cell clones with high, medium, and low CLDN18.2 expression via purified NK cells[1].
ZL-1211 (0.1 μg/mL; 20 min) potently induces complement-dependent cytotoxicity (CDC) against MIA-PaCa2-hCLDN18.2 cell clones with high and moderate CLDN18.2 expression via serum complement[1].
ZL-1211 (at serially diluted concentrations) potently induces antibody-dependent cell-mediated cytotoxicity (ADCC) against gastric cancer cell lines with high (SNU601), moderate (SNU620), and low (KATOIII) endogenous CLDN18.2 expression via purified NK cells at E:T ratios of 1:1 and 3:1. Its efficacy is significantly superior to that of clinical benchmark analogs, and it shows no activity against CLDN18.2-negative SNU5 cells[1].
ZL-1211 (0.01 μg/mL; 3 days) activates NK cells co-cultured with SNU601 gastric cancer cells, as evidenced by a significant increase in intracellular perforin levels compared with the control hIgG1[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:CLDN18.2-overexpressing NUGC4-hCLDN18.2, peripheral blood mononuclear cell (PBMC) effector cells
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Concentration:serially diluted concentrations (cytotoxicity assessment)
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Incubation Time:4-5 hours (incubation at 37°C)
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Result:Induced robust ADCC-mediated tumor cell death, with greater potency than ZL-1211 wild-type Fc and the benchmark analog.
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Cell Line:CLDN18.2-high, -medium, -low MIA-PaCa2-hCLDN18.2
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Concentration:0.1 μg/mL (CDC induction in high/medium clones)
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Incubation Time:20 minutes (pre-incubation at room temperature); 30 minutes (incubation at 37°C with complement)
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Result:Induced CDC-mediated tumor cell death in CLDN18.2-high and -medium clones at 0.1 μg/mL, while the benchmark analog required a much higher concentration to induce CDC.
ZL-1211 (10 mg/kg; i.p.; once weekly) exhibits significant antitumor efficacy against CLDN18.2-low-expressing KATOIII gastric cancer tumors in Balb/c nude mice[1].
ZL-1211 (5 mg/kg; i.p.; once weekly) exerts NK cell-dependent antitumor efficacy against CLDN18.2-highly expressing SNU601 gastric cancer in Balb/c nude mice[1].
ZL-1211 (50 mg/kg; i.p.; three times per week) exerts dose-dependent anti-tumor efficacy against CLDN18.2-expressing gastric cancer PDX models in Balb/c nude mice, while enhancing NK cell infiltration into responsive tumors[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Balb/c nude mice (7-9 weeks old, female)[1]
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Dosage:0.1 mg/kg; 1 mg/kg; 10 mg/kg
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Administration:i.p.; once weekly
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Result:Suppressed SNU620 tumor growth at all tested doses.
Achieved significant tumor inhibition at 0.1 mg/kg, 1 mg/kg, and 10 mg/kg doses at day 42, with similar inhibition to benchmark antibody at 10 mg/kg despite having ~twice lower serum exposure than the benchmark.
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Animal Model:Balb/c nude mice (7-9 weeks old, female)[1]
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Dosage:10 mg/kg
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Administration:i.p.; once weekly
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Result:Significantly suppressed KATOIII tumor growth, with smaller mean tumor volumes compared to the benchmark antibody at day 40.
Did not inhibit growth of CLDN18.2-negative SNU5 tumors.
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Animal Model:Balb/c nude mice; NOD.SCID mice; NCG mice[1]
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Dosage:5 mg/kg
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Administration:i.p.; once weekly
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Result:Significantly suppressed SNU601 tumor growth in Balb/c nude mice, with mean tumor volumes ~50% lower than control at day 60.
Showed minimal to no tumor growth inhibition in NOD.SCID mice and NCG mice, correlating with tumor NK cell levels.
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Animal Model:Balb/c nude mice[1]
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Dosage:50 mg/kg
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Administration:i.p.; three times weekly
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Result:Induced tumor growth inhibition (TGI) in 3 of 7 PDX models: GA0006 (TGI = 56.6%), GA6831 (TGI = 56.0%), and GA2419 (TGI = 40.3%).
No significant TGI was observed in CLDN18.2-negative PDX models.
Increased NK cell density significantly in treated tumors compared to control in the responder PDX group.
CLDN18.2
Unconjugated
The product can be reconstituted/diluted with sterile PBS or saline.
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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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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
ZL-1211 Related Classifications
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