Chemoimmunotherapy for melanoma with dacarbazine and 2,4-dinitrochlorobenzene: results from a murine tumour model.
An empirically established chemoimmunotherapy that combines the epifocal application of the contact sensitizer dinitrochlorobenzene (DNCB) to cutaneous metastases with the systemic administration of dacarbazine (DTIC) yields high response rates and results in prolonged survival. However, despite the fact that this therapy has been in clinical use for several years, the mode of action still remains elusive. In order to overcome this limitation we established a murine model system. B16 melanoma cells were implanted subcutaneously in syngeneic C57BL/6 mice and treatment was started 7 days after. In a first set of experiments mice received intraperitoneal injections of DTIC followed by epifocal applications of DNCB 24 h later. Treatment significantly decreased tumour growth. In contrast, no significant effect was induced by DTIC or DNCB alone. Using this regimen, with varying doses of either DTIC or DNCB, we demonstrated that the therapeutic effect is dose dependent. Furthermore, the treatment of subcutaneous tumours with DTIC and DNCB influenced the course of visceral metastases: the growth of pulmonary metastases was significantly inhibited if subcutaneous tumours were treated as described. In conclusion, we have established a model system that seems to be appropriate for both the optimization of this therapeutic regimen and the characterization of effector mechanisms.
Wack
C
C
Department of Toxicology, Julius-Maximillians-University of Würzburg, Versbacher Strasse 9, D-97078 Würzburg, Germany.
Becker
J C
JC
Bröcker
E B
EB
Lutz
W K
WK
Fischer
W H
WH
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000627:therapeutic use*; D004137:Dinitrochlorobenzene / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007167:Immunotherapy / Q000379:methods*; D007509:Irritants / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000378:metabolism; D008546:Melanoma, Experimental; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D009374:Neoplasms, Experimental / Q000378:metabolism; D013997:Time Factors
D018906:Antineoplastic Agents, Alkylating; D004137:Dinitrochlorobenzene; D007509:Irritants; D003606:Dacarbazine