Active immunotherapy with ultraviolet B-irradiated autologous whole melanoma cells plus DETOX in patients with metastatic melanoma

Omar Eton, Dmitri D. Kharkevitch, Mary Ann Gianan, Merrick I. Ross, Kyogo Itoh, Michael W. Pride, Cherrie Donawho, Antonio C. Buzaid, Paul F. Mansfield, Jeffrey E. Lee, Sewa S. Legha, Carl Plager, Nicholas E. Papadopoulos, Agop Y. Bedikian, Robert S. Benjamin, Charles M. Balch

Research output: Contribution to journalArticlepeer-review

Abstract

Our objective was to determine the clinical activity, toxicity, and immunological effects of active immunotherapy using UVB-irradiated (UVR) autologous tumor (AT) cells plus adjuvant DETOX in metastatic melanoma patients. Eligibility included nonanergic patients fully recovered after resection of 5 or more grams of metastatic melanoma. Treatment consisted of intradermal injections of 107 UVR-AT plus 0.25 ml of DETOX every 2 weeks x 6, then monthly. Peripheral blood mononuclear cells (PBMCs) were harvested for cytotoxicity assays, and skin testing was performed for delayed-type hypersensitivity (DTH) determinations before the first, fourth, seventh, and subsequent treatments. Forty-two patients were treated, 18 in the adjuvant setting and 24 with measurable disease. Among the latter group, there were two durable responses in soft-tissue sites and in a bone metastasis. Treatment was well tolerated. Thirty-five patients were assessable for immunological parameters; 10 of these patients, including the 2 responders, demonstrated early induction of PBMC cytotoxicity against AT cells that persisted up to 10 months on treatment before falling to background levels. In five of seven patients, the fall-off heralded progressive disease. Late induction of a weak DTH reaction to AT cells was observed in eight patients. Active immunotherapy with UVR-AT + DETOX had modest but definite clinical activity in advanced melanoma. The induction of both PBMC cytotoxicity and DTH reactivity to AT cells supported a specific systemic immune effect of treatment, although the former more closely followed disease course in this study.

Original languageEnglish (US)
Pages (from-to)619-627
Number of pages9
JournalClinical Cancer Research
Volume4
Issue number3
StatePublished - Mar 1998
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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