XmAb13676 (anti-CD20/CD3) is an investigational immunotherapy being developed by Xencor to treat blood cancers, including non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

How XmAb13676 works

Blood cancers can be caused by the abnormal behavior and fast growth of B-cells, a type of white blood cell. The protein CD20, found on the surface of B-cells, is a “tumor-associated antigen” (TAA) as it is often over-produced by many B-cell-associated cancers. An antigen is a substance not normally found in the body, and for this reason can be used by the immune system to identify and target abnormal cells, such as cancer cells.

XmAb13676 is a type of immunotherapy, meaning it acts to direct the immune system to recognize and kill cells expressing a certain protein. It is a bispecific antibody, a protein designed to bind to two specific targets simultaneously — in this case, CD20 and CD3.

CD3 is part of a complex of proteins found on the surface of immune cells called T-cells and is involved in their activation. When activated, T-cells can be directed to recognize and kill cells.

When XmAb13676 binds to both CD3 and CD20, it forms a direct link between the T-cell and the tumor cell. This should lead to the activation of the cell-killing ability of T-cells, and direct the toward connected tumor cells.

This direct T-cell and tumor cell link may be able to overcome mechanisms that cancer cells have developed to evade detection by the immune system and increase the rate of T-cell activation specifically at tumor sites.

XmAb13676 in clinical trials

Xencor, in collaboration with Chiltern International, is carrying out an open-label Phase 1 study (NCT02924402) to investigate the safety and tolerability of XmAb13676. The study is ongoing at two sites in the U.S: the MD Anderson Cancer Center in Texas and the Swedish Cancer Institute in Washington. It aims to recruit 66 patients with NHL, CLL, and SLL.

During the trial, XmAb13676 will be administered as an injection into a vein once a week for up to eight weeks. Patients will be monitored for adverse events over the trial’s 56 days, with the aim of testing the safety and tolerability of the treatment. The trial will also determine the maximum tolerated dose (MTD)that might be recommended for potential future trials of XmAb13676.

Other information

Xencor announced that it is collaborating with Novartis to further develop XmAb13676 in June 2016.  Under the agreement, Xencor retains rights to the treatment within the U.S.


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