In a paper published in the July 15 issue of the journal Clinical Cancer Research, the Harvard research team documented tumor regression in two breast cancer patients, and stabilization and containment of tumor growth in late stage breast and kidney patients through application of customized vaccinations made from the patients' own tumor and immune system cells.
By fusing patients' tumor cells with their immune system dendritic cells, researchers associated with the laboratory of Donald Kufe, M.D., professor of medicine at Dana-Farber Cancer Institute and Harvard Medical School, created customized antigen-presenting immune cells that train T cells to hunt, recognize and destroy the patients' tumor cells.
The study group included 23 patients--10 people with breast cancer and 13 with kidney cancer--from whom the researchers were able to collect enough cells to construct fusion cells in the laboratory. The effect of the vaccine on the patient's immune system was measured by the number of circulating T cells that reacted with the patient-derived tumor cells before and after vaccination. Vaccination induced a doubling of tumor reactive T cells in about half the 18 patients in which this was measured. Ten patients doubled the percentage of CD4+ T cells that produced interferon gamma, a cytokine integral to the immune response. Seven patients doubled the percentage of CD8+ T cells that produced the interferon in response to exposure to the tumor.
A third of the study participants responded positively to the customized therapy. Among the breast cancer patient to be immunized, one woman responded to the trial vaccination with 80 percent regression of her chest wall tumor mass within a month. After four months, the tumor had regressed by 90 percent. She remained stable with no evidence of progression during the following two years. A second patient responded with regression of half a tumor that had spread to her adrenal gland, and almost half a pulmonary nodule as well. That individual showed resumed disease progression after a half year. A third breast cancer patient, and five kidney cancer patients, remained stable for three to nine months after completion of the vaccination treatments.
While the results were not universal to all the study participants, Avigan said that that further development of the vaccination, and application on patients with less advanced disease and whose immune systems were less severely weakened, may increase the positive results observed in the Harvard group's initial Phase I trail.
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