A CASE-REPORT - IMMUNE-RESPONSES AND CLINICAL COURSE OF THE FIRST HUMAN USE OF GRANULOCYTE MACROPHAGE-COLONY-STIMULATING-FACTOR-TRANSDUCED AUTOLOGOUS MELANOMA-CELLS FOR IMMUNOTHERAPY/

The first use of e/macrophage-colony-stimulating-factor-transduced, le thally irradiated, autologous melanoma cells as a therapeutic vaccine in a patient with rapidly progressive, widely disseminated malignant m elanoma resulted in the generation of a novel antitumour immune respon se associated with partial, albeit temporary, clinical benefit. An ini tially negative reaction to non-transduced, autologous melanoma cells was converted to a delayed-type hypersensitivity (DTH) reaction of inc reasing magnitude following successive vaccinations, While intradermal vaccine sites showed prominent dendritic cell accrual, DTH sites reve aled a striking influx of eosinophils in addition to activated/memory T lymphocytes and macrophages, recalling the histology of challenge tu mour cell rejection in immune mice, Cytotoxic T lymphocytes (CTL) reac tive with autologous melanoma cells were detectable at high frequency after vaccination, not only in limiting-dilution analysis, but also in bulk culture without added cytokines. Clonal analysis of CTL showed a conversion from a purely CD8+ response to a high proportion of CD4+ c lones following vaccination. A prominent acute-phase response manifest ed by a five- to tenfold increase in C-reactive protein was observed, as was a systemic eosinophilia. Vaccination resulted in the regression of axillary lymphatic metastases, stabilisation of pulmonary metastas es, and a dramatic, reversible increase in cerebral oedema associated with multiple central nervous system metastases; however, lesions in t he adrenal glands, pancreas and spleen proved refractory. The antitumo ur effects and immune response were not detectable 2 months following the last vaccination. Irradiation of the extensive cerebral metastases resulted in rapid deterioration and death of the patient.