Introduction of Obinutuzumab

Obinutuzumab, previous known as afutuzumab, is a humanized IgG1κ type monoclonal antibody that targets CD20 antigen. CD20 has been found to play an important role in B cell-related diseases. This drug was originated by GlycArt Biotechnology AG and developed by Roche as a cancer treatment. Obinutuzumab has been used for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL) in combination with chlorambucil, and for the treatment of patients with patients with follicular lymphoma (FL) who have had prior therapy with the rituximab-containing regimen in combination with bendamustine. Obinutuzumab was approved by the U.S. Food and Drug Administration (FDA) under the trade name Gazyva in 2013, and as Gazyvaro by the European Medicines Agency in Europe in 2014. In addition, it also received the Therapeutic Goods Administration (TGA) approval and Canada health approval in 2014.

Mechanism of Action of Obinutuzumab

Obinutuzumab is the active substance in Gazyvaro and has been designed to recognize and attach to the protein CD20, which was expressed in 90% of B lymphoma cells and normal B lymphoid cells, but not in hematopoietic stem cells, primary B lymphoid cells, normal blood cells, and other normal tissues. Cancerous B-lymphocytes multiply too quickly and replace the normal cells in the bone marrow (where blood cells are made) and in lymph nodes in patients with chronic lymphocytic leukemia and follicular lymphoma. Thus, by binding to CD 20 molecular on the B-lymphocytes, obinutuzumab induces the human immune system to attack B-lymphocytes and clears it in the body. However, stem cells can re-differentiate into B lymphocytes after the body clears B lymphocytes after the treatment because there is no CD20 in stem cells. This allows the body to regain immunity. In contrast to the classic type I CD20 antibody, rituximab, obinutuzumab binds to type II CD20 antibodies. This binding allows obinutuzumab to have a much higher induction of antibody-dependent cytotoxicity and a higher direct cytotoxic effect compared with the classic CD20 antibodies.

Fig.1 Mechanism of action of obinutuzumab

Table 1. Clinical Projects of Obinutuzumab *

Table 2. Approved Drugs of obinutuzumab**

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Reference
* The table was excerpted from the following website
https://clinicaltrials.gov/ct2/results?term=obinutuzumab

** Information presented in the table were collected from the following website:
https://www.ema.europa.eu/en/medicines/human/EPAR/gazyvaro
http://www.pmda.go.jp/PmdaSearch/iyakuSearch/

For research use only. Not intended for any clinical use.