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Treatment of metastatic melanoma with autologous, hapten-modified melanoma vaccine: regression of pulmonary metastases.

Abstract：

: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.

journal_name

Int J Cancer

journal_title

International journal of cancer

authors

Berd D,Sato T,Cohn H,Maguire HC Jr,Mastrangelo MJ

doi

10.1002/ijc.1506.abs

keywords:

subject

Has Abstract

pub_date

2001-11-01 00:00:00

pages

531-9

issue

eissn

0020-7136

issn

1097-0215

pii

10.1002/ijc.1506

journal_volume

pub_type

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Treatment of metastatic melanoma with autologous, hapten-modified melanoma vaccine: regression of pulmonary metastases.