Ocrelizumab

Overview

Ocrelizumab (trade name Ocrevus) is a humanized monoclonal antibody (mAb) for the treatment of CD20-expressing tumors. The Fc engineered Ocrelizumab has overlapping epitopes with rituximab, but shows less immunogenicity and increased antibody-dependent cell-mediated cytotoxicity (ADCC) effect. Therefore, ocrelizumab is considered to be more effective and better-tolerated than rituximab. It is now being evaluated in phase III clinical trials in patients with relapsing-remitting multiple sclerosis (RRMS).

ADCC Enhancement Technology for Ocrelizumab

Ocrelizumab is a novel Fc-engineered anti-CD20 mAb developed to meet the needs of a new therapiy with higher activity on CD20-positive cancers. Compared to the classical rituximab, Ocrelizumab IgG1 shows increased binding to FcγR, greater ADCC potency, and a maximum cytotoxicity than rituximab replacement with the wild-type Fc domain.

Fc-optimized ocrelizumab vs rituximab. Fig.1 Fc-optimized ocrelizumab vs rituximab.

Mechanism of Action of Ocrelizumab

Ocrelizumab is a mAb derived from a parent antibody—rituximab. Ocrelizumab and rituximab bind to the same epitope of CD20 and exhibit similar affinity, tumor orientation, effector cell-independent, anti-tumor cell proliferation activity in breast cancer cells in vitro. Fc-engineered Ocrelizumab is thought to have therapeutic activity against CD20-positive tumors because of:

(A) Binding to CD20 on the surface of B cells to activate complement cascade and produce a membrane attack complex (MAC) that directly induces B cell cleavage by complement-mediated cytotoxicity (CDC).
(B) Interaction with NK cells via Fc receptor III (FcRIII), which results in ADCC effect.

Mechanisms of action of Ocrelizumab.Fig.2 Mechanisms of action of Ocrelizumab.

ADCC Activity

Ocrelizumab

Ocrelizumab in Preclinical

Ocrelizumab efficiently consume peripherally immature and mature B cells. B cell complementation kinetics accelerates when active immunization, and the clinical effect of B cell depletion is depended on the experimental autoimmune encephalomyelitis (EAE) model used.

Ocrelizumab

Ocrelizumab in Clinical Trial

Ocrelizumab

Ocrelizumab

Ocrelizumab

Clinical Development Status

NCT ID Status Conditions Lead Sponsor Phase Update Time
NCT03691077 Recruiting Multiple Sclerosis Assistance Publique - Hôpitaux de Paris Phase 3 December 7, 2018

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

References

  1. Antonio.; et al. B-Cell Therapies in Relapsing Remitting and Primary Progressive Multiple Sclerosis: A Short Clinical Review Spectrum of Disease Progression in Multiple Sclerosis. September 2016.
  2. Mulero P.; et al. Ocrelizumab: a new milestone in multiple sclerosis therapy. Therapeutic Advances in Neurological Disorders. 2018, 11:175628641877302.
  3. Montalban X.; et al. Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis. New England Journal of Medicine. 2017, 376(3):209-220.
  4. Darius H.; et al. Functional characterization of reappearing B cells after anti-CD20 treatment of CNS autoimmune disease. Proceedings of the National Academy of Sciences. 2018:201810470.

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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