Abstract
Natural killer (NK) cell activity and lymphokine activated killer (LAK) cell cytotoxicity were measured in patients receiving recombinant interleukin 2 (rIL-2) and flavone acetic acid (FAA) for treatment of progressing metastatic melanoma. NK activity was increased in 23 of 26 patients and LAK activity induced in 13 of 26 patients. However, levels of cytotoxicity in the present study were not significantly greater than a previous study using rIL-2 alone. LAK cell precursors demonstrated by in vitro incubation of pretreatment lymphocytes with IL-2 and subsequent cytotoxicity were no different in the patients compared to normal controls. Analysis of cell surface phenotypes failed to reveal any significant changes in the cell populations examined, including IL-2R and Leu 19. Although five patients had tumour response, one being complete, there was no correlation with the immunological parameters examined.
Highlights
'Immunology Laboratory, Paterson Institute for Cancer Research and 2CRC Department of Medical Oncology, Christie Hospital and Holt Radium Institute, Manchester M20 9BX, UK
On the basis of these properties of flavone acetic acid (FAA), a phase II clinical trial of FAA in combination with intrasplenic and intravenous recombinant interleukin 2 (rIL-2) was initiated in patients with progressing malignant melanoma and in this report the immunological responses that resulted from this treatment are described
Twenty-six of the 34 patients entered into the phase II trial were subjected to immunological analysis and Table I summarises the clinical response of the group studied for Natural killer (NK) and lymphokine activated killer (LAK) activity
Summary
Several studies have shown that the administration of interleukin 2, either alone or in conjunction with broadly cytotoxic lymphokine activated killer cells (LAK) generated by in vitro co-culture with IL-2 have resulted in tumour regression in a range of established human tumours including melanoma (Rosenberg et al, 1987; Rosenberg, 1988; West et al, 1987; Hank et al, 1988) This combined adoptive immunotherapy is, expensive and labour intensive, and toxicity is severe when high doses of IL-2 are used. Flavone acetic acid (FAA) is a synthetic flavonoid found to have an antitumour effect against a spectrum of murine solid tumours and to augment natural killer cell activity in spleen and other tissues in normal mice (Finlay et al, 1988; Zaharko et al, 1986; Ching & Baguley, 1987) This suggested that FAA may act as a biological response modifier as well as functioning as a chemotherapeutic drug. On the basis of these properties of FAA, a phase II clinical trial of FAA in combination with intrasplenic and intravenous rIL-2 was initiated in patients with progressing malignant melanoma and in this report the immunological responses that resulted from this treatment are described
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