A human
cancer vaccine composed of autologous
tumor cells modified with the
hapten dinitrofluorobenzene (DNP) induces cell-mediated immunity to the
tumor cells and the development of inflammatory responses within metastatic sites. In this study we determined whether DNP
vaccine could induce regression of established
metastases. Ninety-seven patients (83 evaluable) with surgically incurable metastatic
melanoma were treated with DNP
vaccine preceded by low-dose
cyclophosphamide.
Tumor regression was assessed by standard criteria. The development of cell-mediated immunity to
melanoma-associated
antigens was measured by delayed-type
hypersensitivity (DTH) testing before and after DNP
vaccine treatment. Survival analysis was performed by the Kaplan-Meier method. There were 11 antitumor responses: 2 complete, 4 partial and 5 mixed. Both complete responses and 2 of the 4 partial responses occurred in patients with lung
metastases. Response durations were as follows: partial responses-5, 6, 8 and 47+ months; and complete responses-12 and 29 months.
Tumor regression required at least 4 months to become evident and in 2 cases maximum regression was not observed until 1 year after beginning treatment. Patients who exhibited
tumor regression survived longer than those who did not (median survival times: responders, 21.4 months; non-responders, 8.7 months; p = 0.010). DTH to DNP-modified and unmodified autologous
melanoma cells was induced in 87% and 42% of patients, respectively. The DTH response to unmodified cells was significantly associated with prolonged survival. Autologous DNP-modified
melanoma vaccine can induce clinically meaningful regression of
metastases and small lung
metastases appear to be unusually sensitive. The development of DTH to unmodified, autologous
tumor cells may be an important
indicator of the
vaccine's efficacy.