Rochester Researchers Show Proof of Rituximab’s ‘Vaccine’ Effect

March 25, 2009

Steven H. Bernstein, M.D., co-director of Wilmot's lymphoma biology program

The drug rituximab may have an effect against follicular lymphoma (FL) similar to that of a vaccine against the flu, which may help to explain why the drug continues to work in some people long after a single treatment course, according to James P. Wilmot Cancer Center researchers.

Rituximab, a monoclonal antibody, has improved overall survival in FL but the way it works, or its mechanism of action, has not been completely defined. In the journal Blood, published electronically in February, the Rochester group provided the first-ever “proof of principle” that rituximab elicits an active immune response from FL-specific T cells.

Steven H. Bernstein, M.D., lead author of the study and co-director of Wilmot’s lymphoma biology program, said the vaccine effect is likely the result of many complex and interacting cellular mechanisms, ultimately resulting in the inflammatory death of lymphoma cells. Additional studies with more patients are needed to show the correlation of immune responses to clinical responses.

In the present study, however, Bernstein’s group, led by Shannon Hilchey, Ph.D., looked at five patients and analyzed the immune response against the immunoglobin expressed by the follicular lymphoma before and after rituximab therapy. After treatment, four of the five patients showed an increase in cancer-fighting FL-specific T cells.

“The demonstration that rituximab generates an active lymphoma specific immune response could have profound implications as to how we optimally treatment patients with follicular lymphoma,” the paper stated. Specifically, if doctors can boost the immunological memory of the T cell response, patients might live longer.

Rituximab may marshal the body’s natural defenses to attack the malignant cells, but the challenge, Bernstein said, will be to overcome the way FL tumors fight back by suppressing the immune system.

Follicular lymphoma is the second most common form of non Hodgkin’s lymphoma in the United States, and affects more than 15,000 people per year. Like other lymphomas it has significantly increased in incidence over the past three decades. Approximately 20 percent of the patients are diagnosed at early stages.

New therapies such as rituximab, in combination with chemotherapy, have significantly improved overall survival in the past decade are now routinely incorporated into treatment regimens.

The Lymphoma Research Foundation Follicular Lymphoma Research Grant, and a SPORE in Lymphoma Grant, funded the research. Rituximab, which is known by the brand name Rituxan, is made by Genentech; Bernstein is a member of the Genentech Speakers Bureau.

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