TrasGEX

Overview

TrasGEX (alternative names: Glycooptimised TrastuzuMab-GEX; GT-Mab 7.3-GEX; TrasGEX; TrastuzuMab-GEX) is an anti-HER2 mAb that exhibits increased binding affinity for all FcγRIIIa variants expressed on immune effector cells. Compared to its parent antibody—trastuzumab, defucosylated TrasGEX showed significantly improved cell killing in ADCC-based assays and a higher activity in models in vivo. In addition, TrasGEX is currently being evaluated in clinical phase II trials and has shown good clinical activity in patients with HER2-positive solid tumors.

ADCC Enhancement Technology for Trastuzumab

TrasGEX is a second-generation glycosylated antibody developed to meet the needs of a new therapy exhibiting higher activity on Her2-positive cancers. The glycosylation process used to develop this agent is achieved by reducing the fucosylation in the Fc region of the mAb molecule, resulting in increased binding affinity of the agent for the FcγRIII receptor on immune effector cells.

Mechanism of Action of Trastuzumab

TrasGEX is derived from a parent antibody—trastuzumab. TrasGEX and trastuzumab bind to the same epitope of HER2 and thus, allow for competition and substitution between these two antibodies. Similar to the MOA of trastuzumab, glyco-engineered TrasGEX is thought to exhibit its therapeutic activity against HER2-positive tumors because of:

Mechanism of action of Trastuzumab. Fig.1 Mechanism of action of Trastuzumab.

Glycan Analysis

TrasGEX

Binding Affinity Characterization

TrasGEX

ADCC Activity

TrasGEX

Preclinical Research

TrasGEX

Clinical Anti-tumor Activity

TrasGEX

TrasGEX

TrasGEX

Clinical Development Status

NCT ID Status Conditions Lead Sponsor Phase Update Time
NCT01409343 Completed Solid Tumors Glycotope GmbH Phase 1 December 20, 2013

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References

  1. Junttila TT.; et al. Superior In vivo Efficacy of Afucosylated Trastuzumab in the Treatment of HER2-Amplified Breast Cancer. Cancer Research. 2010, 70(11):4481-4489.
  2. Walter F.; et al. Phase I study of TrasGEX, a glyco-optimised anti-HER2 monoclonal antibody, in patients with HER2-positive solid tumours[J]. ESMO Open, 2018, 3(4):e000381.
  3. Fiedler W.; et al. Phase I study of TrasGEX, a glyco-optimised anti-HER2 monoclonal antibody, in patients with HER2-positive solid tumours. ESMO Open. 2018, 3(4), e000381. doi:10.1136/esmoopen-2018-000381.

RESOURCES

Creative Biolabs provides luciferase-based ADCC assay. This Jurkat cell based assay is pioneered by Creative Biolabs, and the methodology is very well accepted by the field. See attached ADCC Reporter Assay Protocol for further details. 

All products and services are for Research Use Only. Do Not use in humans.

CASE STUDY

ADCC Assay WT vs AfucoTM Mabs  Visit

Resource

Antibody Fc Engineering: Towards Better Therapeutics  Visit

ONLINE INQUIRY

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