Xaluritamig
Based on 1 Customer Validation
Xaluritamig (AMG-509) is a bispecific T cell engager and cytolytic agent with a Kd of 27.6 nM for human CD3ε. Xaluritamig binds to CD3ε via an anti-CD3 single-chain variable fragment (scFv) domain, and to STEAP1 via a bispecific anti-STEAP1 antigen-binding fragment (Fab) domain, thereby recruiting and activating T cells and forming a bridge between T cells and STEAP1-expressing cancer cells. Xaluritamig induces T cell-mediated redirected cytotoxicity, tumor cell lysis, cytokine release, CD8+ T cell activation and expansion, as well as tumor stasis or regression. Xaluritamig contains an Fc domain with no effector function, which prolongs serum half-life, exhibits only minimal activity against cells with low STEAP1 expression and normal cells, and shows extremely low target-related off-tumor toxicity in cynomolgus monkeys. Xaluritamig is used in STEAP1×CD3 XmAb 2+1 immunotherapy and in research on metastatic castration-resistant prostate cancer and Ewing sarcoma.
For research use only. We do not sell to patients.
- Purity: ≥99%
- CAS No.: 2559056-68-5
- Molecular Weight:173.555 kDa
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
half-IgG1-kappa/VH-CH1-h-(scFv-heavy-lambda)-h-CH2-CH3
Human
CD3E & STEAP1
Xaluritamig (AMG-509) binds specifically to 293T cells transfected with human STEAP1, with an EC50 of 3.8 nM[2].
Xaluritamig potently induces T cell-mediated lysis of STEAP1-positive human cancer cells, with a median EC50 of 37 pM across 19 cell lines; it shows no activity against STEAP1-knockout prostate cancer cells[2].\n
Xaluritamig redirects prostate cancer cell lysis with higher potency than the anti-STEAP1 Fab XmAb molecule alone; it preferentially kills cancer cells with high STEAP1 expression and exhibits extremely low activity against normal cells[2].
Xaluritamig induces only extremely low levels of cytotoxicity in STEAP1-low-expressing human normal bronchial smooth muscle cells and aortic endothelial cells cultured in vitro[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Xaluritamig (0.3 mg/kg; intravenous injection; administered twice at a 7-day interval; total duration of 17 days) significantly inhibits tumor growth in the tibial bone metastasis model of Myc-CaP-LucSTEAP1 in FVB/N huCD3ε knock-in mice, but its combination with anti-PD-1 antibody does not enhance anti-tumor activity[4].
Xaluritamig (10 μg/kg, or an additional 40 μg/kg; intravenous injection; for 28 consecutive days) is well tolerated in male and female Mauritian-origin cynomolgus monkeys. Serum exposure is nearly dose-proportional, with no serious target-related off-tumor toxicity[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Male NSG mice (NOD.Cg-Prkdcscid Il2rgtm1N/j/SzJ), no specified weight and age + 22Rv1-LucSTEAP1 subcutaneous xenograft model[4]
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Dosage:0.01 mg/kg, 0.1 mg/kg, 1 mg/kg
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Administration:Intravenous injection; twice, 7 days apart; 16 days.
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Result:Exerted significant antitumor activity.
The 0.01 mg/kg dose achieved 99.7% tumor growth inhibition with complete tumor stasis, while the 0.1 mg/kg and 1 mg/kg doses induced 61.6% and 66.2% tumor regression, respectively, after two administrations on days 9 and 16.
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Animal Model:Male and female cynomolgus monkeys (Mauritian origin), normal toxicology evaluation model[4]
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Dosage:10 μg/kg flat dose, 10 μg/kg initial dose followed by 40 μg/kg weekly
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Administration:Intravenous injection; single-dose group: once; step-dose group: four times; 28 days.
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Result:Was well tolerated during the 28-day study, with nearly dose-proportional and no gender differences in serum exposure.
Transient changes related to acute phase response were observed, including increased C-reactive protein, decreased absolute counts of total T cells, cytotoxic T cells, helper T cells and natural killer cells, and mild increases in neutrophils and globulins.
No severe target-related off-tumor toxicity was detected.
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Unconjugated
The product can be reconstituted/diluted with sterile PBS or saline.
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half-IGG1-kappa/VH-CH1-h-(scFv-heavy-lambda)-h-CH2-CH3
ELISA, FACS, Functional assay
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Flow cytometric analysis of 1X106 Jurkat cells with Xaluritamig (HY-P990688, red). Cells were fixed with 4% paraformaldehyde. Then stained with the primary antibody at 1/200 dilution for an hour at 4℃. Alexa Fluor 488-conjugated AffiniPure Goat Anti-Human IgG H&L (HY-P83776) was used as the secondary antibody at 1/1,000 dilution for 30 minutes at 4℃. Human IgG1 kappa (HY-P99001, blue) was used as the isotype control, cells without incubation with primary antibody were used as the unlabeled control (black). -
Flow cytometric analysis of 1X106 FaDu cells with Xaluritamig (HY-P990688, red). Cells were fixed with 4% paraformaldehyde. Then stained with the primary antibody at 1/200 dilution for an hour at 4℃. AF 488-conjugated AffiniPure Goat Anti-Human IgG H&L (HY-P83776) was used as the secondary antibody at 1/1,000 dilution for 30 minutes at 4℃. Human IgG1 kappa (HY-P99001, blue) was used as the isotype control.
Chemical Information
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CAS No. 2559056-68-5
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Appearance Liquid
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Molecular Weight 173.555 kDa
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Color Colorless to light yellow
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Synonyms
AMG-509
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Shipping
Shipping with dry ice.
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Formulation
Please refer to the lot-specific COA for specific buffer information.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
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Data Sheet (264 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Inhibitory Antibodies User Guide (603 KB)
References
[1]. Kelly WK, et al. Xaluritamig, a STEAP1 × CD3 XmAb 2+1 Immune Therapy for Metastatic Castration-Resistant Prostate Cancer: Results from Dose Exploration in a First-in-Human Study. Cancer Discov. 2024 Jan 12;14(1):76-89. [Content Brief]
[4]. Nolan-Stevaux O, et al. AMG 509 (Xaluritamig), an Anti-STEAP1 XmAb 2+1 T-cell Redirecting Immune Therapy with Avidity-Dependent Activity against Prostate Cancer. Cancer Discov. 2024 Jan 12;14(1):90-103. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)