RO5083945

Overview

RO5083945 (or GA201, RG7160) is the first glycosylation-modified monoclonal antibody (mAb) directed against the epidermal growth factor receptor (EGFR) for the treatment of cancer and autoimmune diseases. RO5083945 has a fully human glycosylation pattern and is optimized for glycosylation in its Fc domain to promote antibody-dependent cell-mediated cytotoxicity (ADCC). EGFR is overexpressed on the cell surface in a variety of tumor types and acts under several anti-tumor mechanisms: strong ADCC, inhibition of proliferation by receptor blockade, and induction of apoptosis. A clinical phase I dose escalation study involving RO5083945 is ongoing to investigate the efficacy of this antibody in the treatment of solid tumors, including KRAS mutant CRC.

ADCC Enhancement Technology for RO5083945

RO5083945 is derived by glycosylation of the parental cetuximab. The glycosylation process used to develop this agent is achieved by altering the glycosylation profile in the Fc region of the mAb molecule, resulting in a significant enhancement of immunogenicity and thus, a stronger ADCC response.

Site-specific glycoengineering of cetuximab for enhanced ADCC activity. Fig.1 Site-specific glycoengineering of cetuximab for enhanced ADCC activity.

Mechanism of Action of RO5083945

Glyco-engineered RO5083945 is thought to have therapeutic activity against EGFR-positive tumors because of:

Mechanism of action of RO5083945.Fig.2 Mechanism of action of RO5083945.

Glycan Analysis of RO5083945

RO5083945

Antigen Binding Characteriztion

RO5083945

ADCC Activity

RO5083945

Preclinical Anti-tumor Activity

RO5083945

RO5083945

Clinical Anti-tumor Activity

RO5083945

Clinical Development Status

NCT ID Status Conditions Lead Sponsor Phase Update Time
NCT00721266 Completed Neoplasms Glycotope GmbH Phase 1 November 2, 2016

For more detailed information, please do not hesitate to contact us.

References

  1. Gerdes CA.; et al. GA201 (RG7160): A Novel, Humanized, Glycoengineered Anti-EGFR Antibody with Enhanced ADCC and Superior In Vivo Efficacy Compared with Cetuximab. Clinical Cancer Research. 2013, 19(5):1126-1138.
  2. Open-label, multicentre expansion cohort to evaluate imgatuzumab in pre-treated patients with KRAS-mutant advanced colorectal carcinoma. European Journal of Cancer. 2014, 50(3):496-505.

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

Creative Biolabs has established a team of customer support scientists ready to discuss ADCC/CDC optimization strategies, antibody production, bioinformatics analysis and other molecular biology/biotechnology issues.

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