Ocaratuzumab

Overview

Ocaratuzumab (AME-133v, LY2469298) is a humanized monoclonal antibody(mAb) directed against human CD20 for the treatment of cancer and autoimmune diseases. The antibody is engineered in the Fc region to enhance its affinity to B lymphocyte CD20 antigen, promote antibody-dependent cell-mediated cytotoxicity (ADCC), and improve treatment of low-affinity FcγRIIIa allotypes. Compared with rituximab, the affinity of ocaratuzumab for CD20 was significantly increased by 13 to 20-fold, and the effective ADCC was increased by 6-fold. The drug is currently being developed by Mentrik Biotech, LLC, and a phase II clinical trial is underway.

ADCC Enhancement Technology for Ocaratuzumab

Ocaratuzumab is a novel Fc-engineered humanized anti-CD20 mAb optimized for superior ADCC. Using single-point codon-substitutions strategy, the amino acid substitutions are engineered into the IgG1 Fc domain, resulting in increased binding to FcγR. Ocaratuzumab has greater ADCC potency and maximum cytotoxicity than rituximab that is replaced in the wild-type Fc domain.

Fc-optimized Ocaratuzumab. Fig.1 Fc-optimized Ocaratuzumab. (Source: Mentrik Biotech, LLC)

Mechanism of Action of Ocaratuzumab

Ocaratuzumab is a secondary mAb derived from a parent antibody—rituximab. Ocaratuzumab and rituximab bind to the same epitope of CD20 and thus, allow for competition and substitution between the two antibodies. Similar to the MOA of rituximab, Ocaratuzumab is thought to mediate its therapeutic activity against CD20-positive tumors by working on ADCC, CDC, and ADCP efficacy. Details are shown in the figure below:

Mechanisms of action of CD20 antibodies. Fig.2 Mechanisms of action of CD20 antibodies.

ADCC Activity

Ocaratuzumab

Ocaratuzumab Binding Characterization

Ocaratuzumab

Preclinical Research

Ocaratuzumab

Ongoing Clinical Trial for Ocaratuzumab

Ocaratuzumab

Ocaratuzumab

Ocaratuzumab

Clinical Development Status

NCT ID Status Conditions Lead Sponsor Phase Update Time
NCT00354926 Completed Non-Hodgkin's Lymphoma Applied Molecular Evolution Phase 1 January 7, 2016

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

Reference

  1. Ganjoo KN.; et al. Phase 1/2 Study of Ocaratuzumab, an Fc-Engineered Humanized Anti-CD20 Monoclonal Antibody, in Low-Affinity FcγRIIIa Patients with Previously Treated Follicular Lymphoma. Leuk Lymphoma. 2015, 56(1):42-48.

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.

  • *
  • *
  • *
USA

UK