dalutrafusp alfa   Click here for help

GtoPdb Ligand ID: 11776

Synonyms: AGEN-1423 | AGEN1423 | GS-1423
Compound class: Antibody
Comment: Dalutrafusp alfa is a bispecific antibody-fusion protein that was designed as a checkpoint modulator for immuno-oncology. It was invented by Agenus (as AGEN-1423), and has been licensed to Gilead for clinical development (as GS-1423). The antibody portion of dalutrafusp targets the adenosine degrading enzyme ecto-5'-nucleotidase (NT5E/CD73; produces an immunosuppressive effect in the tumour micoenvironment), and this is fused via a peptidyl linker to the extracellular domain of transforming growth factor beta receptor 2 (TGFBR2) which acts as a molecular trap for both TGFβ1 and TGFβ3. NT5E and TGFβ are two significant resistance pathways that allow tumours to escape immune surveillance.
In the absence of a peer reviewed disclosure, analysis of patent documents suggests that dalutrafusp alfa may be closely related to the anti-CD73-TGF trap fusion protein BA037 that is claimed in Agenus' patent WO2019173692A2 [1]. The CDRs in the sequences of the anti-NT5E/CD73 mAb region from the dalutrafusp alfa INN document match SEQ IDs presented in the patent.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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Bioactivity Comments
BA037 from WO2019173692A2 binds strongly to TGFβ1 and TGFβ3 peptides in vitro with Kd values of 2.1 pM and 4.2 pM respectively [1]. The binding affinity in the interaction table is the value for BA037 binding to human NT5E (CD73) provided in WO2019173692A2.
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
Ecto-5'-Nucleotidase Hs Antibody Binding 10.2 pKd - 1
⤷ pKd 10.2 (Kd 6.9x10-11 M) [1]