RG7828 (anti-CD20/CD3, also known as BTCT4465A) is an investigational immunotherapy being developed by Genentech, a subsidiary of Roche.

RG7828 is being investigated as a treatment for various types of blood cancer, including non-Hodgkin Lymphoma (NHL) and chronic lymphocytic leukemia (CLL).

How RG7828 works

Blood cancers such as NHL and CLL can be caused by the abnormal behavior and growth of B-cells, a type of white blood cell. Cancerous B-cells often produce in excessive amounts a protein called CD20 on their surface.

As an immunotherapy, RG7828 is a drug designed to encourage the immune system to recognize and target CD20-producing cells as abnormal and unwanted.

The immune system usually kills abnormal cells by directing a type of immune cell, called T-cells, to attack them. However, cancer cells can develop mechanisms to evade detection by the immune system through T-cell inactivation. This results in not enough T-cells being available to eliminate the cancer.

RG7828 is a bispecific antibody. An antibody is a protein designed to bind to a particular target; as a “bispecific” antibody, RG7828 can simultaneously bind to two targets — CD20 on the cancerous B-cells, and CD3, which is part of a complex of proteins expressed on the surface of T-cells and involved in the activation of T-cells that can recognize and attack a specific target.

By binding to both CD3 and CD20, RG7828 crosslinks the T-cell with the tumor cell. This allows the T-cell to recognize the tumor, and should result in the activation of T-cells’ cell-killing ability. Through this mechanism, RG7828 should slow cancer progression and may cause a targeted reduction in tumor size.

Results from preclinical studies in monkey models of disease, published in the journal Science Translational Medicine, demonstrated that RG7828 can successfully reduce the number of B-cells in these models.

RG7828 in clinical trials

Genentech is running an open-label Phase 1 dose-escalation study (NCT02500407) to investigate RG7828, alone or in combination with Tecentriq (atezolizumab), in patients with B-cell NHL and CLL that has returned or is resistant to standard therapy.

The trial’s primary outcome is to determine the maximum tolerated dose of RG7828, with and without Tecentriq, as well as a preliminary assessment of the treatment’s anti-tumor activity. Patients will be monitored for adverse events for up to 14 months, and the percentage of patients responding to the treatment will be recorded for up to three years.

The trial is still recruiting up to 390 patients at multiple sites in the U.S., Australia, Canada, and Korea. Information is available by clicking on its identification number.


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