Monday, December 20, 2010

Mapatumumab: New Antibody for Follicular Lymphoma?

The clinical research field is currently awash with new treatments for follicular lymphoma and other forms of lymphoma. Most of these, of course, will not be marketed, either because they will turn out not to work at all or because they will not be noticeably more effective than alternative treatments. It's still too soon to say where mapatumumab will fit into this picture.

Mapatumumab is a monoclonal antibody drug -- an antibody designed to bind to a specific site on the surface of cells, in this case cancer cells. In this way it is similar to the better-known (and established) drug rituximab (Rituxan, MabThera), which is a standard drug in first-line treatment of follicular lymphoma. Where rituximab targets the CD20 protein, though, mapatumumab goes after a more novel target: Tumour Necrosis Factor-Related Apotosis-Inducing Ligand Receptor 1, Death Receptor 4 -- more simply, TRAIL-R1. Once it binds to that site, it triggers apoptosis -- programmed cell death, a genetic command to self-destruct after suffering damage which cancerous cells normally bypass.

Also unlike the first generation of anti-CD20 agents, like rituximab and Bexxar, mapatumumab is also a fully human antibody rather than being derived from mouse or chimeric (mouse-human hybrid) cellular lines. As with the novel anti-CD20 drug ofatumumab, this may turn out to reduce the risk of severe allergic reactions.

Mapatumumab has been in testing against lymphoma for over five years. It was subsequently tested in solid-tumour cancers, mostly lung cancer, breast cancer, and colon cancer, with some potentially promising results.

In one recent American study by A. Younes et al., 40 patients with varying lymphomas were recruited and randomized to either a low or a high dose of the drug, given over multiple month-long cycles. It involved a higher dose than previous Phase I trials (from 3 to 10 mg/kg-1 per cycle). Overall, 15% of patients responded. 3 of 17 follicular lymphoma patients responded, 1 completely, and a further two had stable disease for about two years. In a Phase I trial, these results are more than intriguing enough to justify further research.

Check out the mapatumumab ticker for all posts on this drug.

Published Research

A. Younes et al. "A Phase 1b/2 Trial of Mapatumumab in Patients with Relapsed/Refractory Non-Hodgkin's Lymphoma."

Sebastian Hotte et al. "A Phase 1 Study of Mapatumumab." Clinical Cancer Research (2008).

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