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Patients' cells from tumors, the immune system merged for customized cancer therapy

cells.

In the past, immunologists have attempted to define cancer specific markers and develop vaccinations with those molecules, but most tumors don't have well-defined antigens that can be isolated or have proved useful for vaccination development. Previous research approaches often were aimed at producing T cells that would recognize a defined cancer marker molecule, but the immune response to those vaccinations often fell short of expectations.

The Harvard team aimed at making a hybrid cell composed of both the cancer cells and dendritic cells taken from patients for use exclusively in the individual from whom the cells were obtained.

"This approach increased the number of antigens that immune system cells can recognize," Avigan said. "And for the individual patients, those antigens are specific to their own tumor cells."

The challenges of the trial included constructing the hybrid cells and evaluating the vaccinations performance in the donor patients. The dendritic cells were obtained from the patients' blood. But harvesting cells from the tumors proved difficult. Cell numbers from individual patients were sometimes too low for successful generation of the hybrid tumor/dendritic cell fusion.

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 t
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Contact: Russell Vanderboom
vanderboom@aacr.org
215-440-9300
American Association for Cancer Research
15-Jul-2004


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