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 |
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| Authors: | K A O Ellem Michael G E O’Rourke Gregory R Johnson Gordon Parry Ihor S Misko Christopher W Schmidt Peter G Parsons Scott R Burrows Simone Cross Andrew Fell Chung-Leung Li John R Bell Philip J Dubois Denis J Moss Michael F Good Anne Kelso Lawrence K Cohen Glenn Dranoff Richard C Mulligan |
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| Institution: | (1) Queensland Cancer Fund Research Unit, Queensland Institute of Medical Research, Bancroft Centre, 300 Heston Road, Brisbane 4029, Queensland, Australia, AU;(2) The Epstein Barr Virus Unit, Queensland Institute of Medical Research, Bancroft Centre, Brisbane, Queensland, Australia, AU;(3) The Malaria and Arbovirus Unit, Queensland Institute of Medical Research, Bancroft Centre, Brisbane, Queensland, Australia, AU;(4) The Transplantation Biology Unit, Queensland Institute of Medical Research, Bancroft Centre, Brisbane, Queensland, Australia, AU;(5) The Leukaemia Foundation of Queensland Daikyo Research Unit, Queensland Institute of Medical Research, Bancroft Centre, Brisbane, Queensland, Australia, AU;(6) Department of Surgery, Mater Adult Public Hospital, Brisbane, Queensland, Australia, AU;(7) Department of Pathology, Mater Adult Public Hospital, Brisbane, Queensland, Australia, AU;(8) Mater Private Hospital M.R.I. Unit, Brisbane, Queensland, Australia, AU;(9) Somatix Therapy Corp., Alameda, California, USA, US;(10) Dana-Farber Cancer Institute and Harvard Medical School, Boston, Mass., USA, US;(11) Whitehead Institute and Department of Biology, Massachusettes Institute of Technology, Cambridge, Mass., USA, US |
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| Abstract: | The first use of granulocyte/macrophage-colony-stimulating-factor-transduced, lethally irradiated, autologous melanoma cells
as a therapeutic vaccine in a patient with rapidly progressive, widely disseminated malignant melanoma resulted in the generation
of a novel antitumour immune response associated with partial, albeit temporary, clinical benefit. An initially negative reaction
to non-transduced, autologous melanoma cells was converted to a delayed-type hypersensitivity (DTH) reaction of increasing
magnitude following successive vaccinations. While intradermal vaccine sites showed prominent dendritic cell accrual, DTH
sites revealed a striking influx of eosinophils in addition to activated/memory T lymphocytes and macrophages, recalling the
histology of challenge tumour cell rejection in immune mice. Cytotoxic T lymphocytes (CTL) reactive 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+ clones following vaccination. A prominent acute-phase response manifested 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 metastases, and a dramatic, reversible increase in cerebral oedema associated with multiple central nervous system
metastases; however, lesions in the adrenal glands, pancreas and spleen proved refractory. The antitumour 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.
Received: 20 September 1996 / Accepted: 5 December 1996 |
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| Keywords: | GM-CSF-transduced autologous melanoma vaccine Cerebral metastases-acute cerebral oedema Tumour-reactive cytotoxic T lymphocytes Eosinophilia C-reactive protein |
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