Amtabafusp alfa  (Synonyms: GS-8588)

Amtabafusp alfa (GS-8588) is an envelope-targeting bispecific T-cell engager for HIV treatment. Amtabafusp alfa redirects effector T cells by binding to CD3 via a humanized anti-CD3 Fab domain and to HIV envelope proteins via an engineered CD4 domain 1 variant. Amtabafusp alfa exhibits potent, broad-spectrum activity against a variety of HIV isolates and specifically kills HIV-infected cells. Amtabafusp alfa can be used for research on HIV infection^[1].

Fusion-half-IGG1-lambda2/CD4-h-CH2-CH3

Human

CD3 & gp120/Glycoprotein 120

Amtabafusp alfa (dilution series) binds to HIV-infected CEM cells, with EC₅₀ values ranging from 6 to 67 nM against 24 subtype B isolates^[1].
Amtabafusp alfa (dilution series) binds to CD4 and CD8 T cells of healthy cynomolgus monkeys and rhesus monkeys with similar potency, with geometric mean EC₅₀ values of 9.9 nM and 12.0 nM, respectively^[1].
Amtabafusp alfa (dilution series) potently kills HIV-infected resting primary CD4 T cells (with a median EC₅₀ of 0.1 μg/mL for 29 out of 32 isolates) and kills the remaining 3 isolates in activated PBMC-based and CEM-based assays^[1].
Amtabafusp alfa (dilution series) shows no detectable binding or cytotoxic effect on MHCII-expressing B cells, but mediates the killing of HIV-infected CD4 cells in the same experiment^[1].
Amtabafusp alfa (10^-8-10⁴ μg/mL) induces low-level CD69 upregulation and cytokine production in peripheral blood mononuclear cells (PBMCs) derived from people with HIV (PWH) during both ART-suppressed viral suppression phase and viremic phase^[1].

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

Amtabafusp alfa (1-100 mg/kg/week; i.v.; single dose, weekly for 5 doses) exhibits IgG-like pharmacokinetics, achieves ~25% lymph node to serum exposure, and is well tolerated with no adverse findings in healthy cynomolgus monkeys at doses up to 100 mg/kg/week, with safety margins >100-fold relative to the projected minimally efficacious dose^[1].

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

P03377 & P07766

ELISA, FACS, Functional assay

Unconjugated

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

2839531-84-7

Liquid

Colorless to light yellow

[GS-8588]

Shipping with dry ice.

Please refer to the lot-specific COA for specific buffer information.

Please store the product under the recommended conditions in the Certificate of Analysis.

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  Fusion-half-IGG1-lambda2/CD4-h-CH2-CH3

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  Loaded GS-8588 on ACH2 biosensor, can bind HY-P76390 envelope glycoprotein gp120 Protein, HIV-1 (AAC31819, HEK293, His) with an affinity constant of 5.260E-09 M as determined in BLI assay.

• [1]. Lam, et al. GS-8588, A novel envelope-targeting bispecific T-cell engager for HIV cure. Abstract presented at the 25th International AIDS Conference (AIDS 2024), Munich, Germany.