Chemoimmunotherapy for melanoma with dacarbazine (DTIC) and dinitrochlorbenzene (DNCB): characterization of the involved mechanisms.
Project management at the University of Würzburg:
Using the murine B16-melanoma model we investigated possible mechanisms involved in the combined chemoimmunotherapy for melanoma with dacarbazine a chemotherapeutic agent and the contact senitizer 2,4-dinitrochlorbenzene. Although this therapy yields high response rates resulting in prolonged survival, the mechanisms involved remain unknown. Previously, we have shown that this therapeutic regimen is active in the murine B16-melanoma model. The data from our present study demonstrate that the combined therapy elicits a specific T cell dependent immune response. In a next set of experiments we scrutinized tumor-infiltrating lymphocytes. Therapy resulted in the clonal expansion of T cells. Transfering lymphoctes from mice treated with DTIC and DNCB in untreated tumor-bearing mice, indicated that T cells migrate to the tumor. In summary, these finding demonstrate the ability of DTIC/DNCB treatment to induce an effective T cell-dependent host immune response against a syngeneic tumor.
An empirically estabilished chemoimmunotherapy for metastatic melanoma combines the systemic administration
Projekt period: from 05.1999 to 04.2002