The current standard of care is rituximab, a drug that targets CD20, a protein receptor that is highly expressed on the surface of lymphoma cells. Half of patients with B-cell lymphoma do not respond to rituximab, however, and those who do eventually relapse. Therefore, according to researchers, the search is on for other antibodies to add to rituximab to increase its efficacy.
Use of an agent called veltuzumab, an anti-CD20 antibody currently under development, along with milatuzumab, an experimental antibody that targets a different receptor called CD74, significantly improved survival in mice who received the monoclonal antibody treatment cocktail, the Garden State team reports. Using mouse models of B-cell lymphoma, they found that treatment with veltuzumab extended median survival time from 36 days in untreated mice to 70 days, and milatuzumab extended median survival time to about 90 days. However, when both agents were used, mice lived a median of 113 days.
The important finding is that we show that using a combination of two antibodies targeting two different receptors on the malignant cells, when the receptors have different functions, leads to an improvement in survival over use of either antibody alone, said Rhona Stein, Ph.D., of the Center for Molecular Medicine and Immunologys Garden State Cancer Center.
This also suggests that if the malignant cells become refractive to one antibody, the other may still be effective, since it can bind to a different receptor, she said.
Both veltuzumab and milatuzumab are naked antibodies − monoclonal antibodies that are not bound to a therapeutic drug or radioisotope − but each latches on to different receptors on the surface of lymphoma cells.
Milatuzumab binds to the CD74 receptor
|Contact: Greg Lester|
American Association for Cancer Research