Fused Dendritic/Cancer Cells Promote Immune Response

n DALLAS—A vaccine for breast cancer patients using fusions of dendritic cells and cancer cells is currently in phase I clinical testing, said Jianlin Gong, MD, Division of Cancer Pharmacology, Dana-Farber Cancer Institute, and instructor in medicine, Harvard Medical School.

Although breast cancer cells carry distinct markers that identify them as abnormal, they somehow escape recognition by the body’s immune system, Dr. Gong said. It is believed that the cancer cells prevent the stimulation of T cells directed against them. Other problems that may prevent the immune system from detecting breast cancer cells include the weak immunogenicity of tumor antigens, the lack of costimulatory signals, and unidentified tumor antigens.

“One exciting approach to effectively induce an antitumor immune response is through the use of potent immune-stimulating cells known as dendritic cells,” Dr. Gong said.

Speaking at the Susan G. Komen Foundation 1999 National Grant Conference, Dr. Gong reported that the fusion cells have been designed to link costimulatory molecules derived from the dendritic cells (essential for activation of T cells) with tumor markers that guide the cells to the tumor.

Mice that were vaccinated with fusion cells did not develop tumors when inoculated with breast cancer cells, while those that did not receive the vaccine before the breast cancer cell inoculation died rapidly. “Most significantly, mice with preexisting breast cancer metastasis in the lungs were cured of the disease after receiving the vaccine,” Dr. Gong said.

The researchers have now successfully fused human dendritic cells with autologous breast cancer cells. “The breast cancer patient’s T cells exhibit strong killing of breast cancer cells after being activated by the fusion cells,” Dr. Gong said.