Immuno Regulation

The team carries out highly focused laboratory efforts in cancer immunotherapy, blending both clinical and laboratory expertise. Dr. Vieweg and his collaborators were the first to demonstrate utility of dendritic cell (DC)-based vaccines for the treatment of prostate and renal cancer. They demonstrated that messenger RNA-pulsed DCs are capable of stimulating potent T-cell responses in vitro as well as in the cancer patient. The group has also pioneered the use of targeted pharmacological interventions to abrogate the immunosuppressive effects of regulatory T cells or myeloid suppressor cells. In one instance, they have shown that a diphtheria fusion protein binding to the high affinity IL-2 receptor (CD25) was capable of eliminating FoxP3+ regulatory T-cell populations in the peripheral blood of renal and prostate cancer patients. Both Dr. Vieweg and Dr. Kusmatsev have provided evidence that “universal antigens” such as human telomerase reverse transcriptase (hTERT) or survivin can function as highly relevant tumor targets in vitro and in vivo systems. Translating these concepts into human settings, administration of hTERT mRNA-transfected DC were capable of stimulating hTERT-specific CD8+ and CD4+ T-cell responses in prostate cancer patients and of reducing circulating tumor cells and PSA velocity in virtually all patients.