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

Ellem, KAO, ORourke, MGE, Johnson, GR, Parry, G, Misko, IS, Schmidt, CW, Parsons, PG, Burrows, SR, Cross, S, Fell, A, Li, CL, Bell, JR, Dubois, PJ, Moss, DJ, Good, MF, Kelso, A, Cohen, LK, Dranoff, G and Mulligan, RC (1997) 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. Cancer Immunology Immunotherapy, 44 1: 10-20. doi:10.1007/s002620050349


Author Ellem, KAO
ORourke, MGE
Johnson, GR
Parry, G
Misko, IS
Schmidt, CW
Parsons, PG
Burrows, SR
Cross, S
Fell, A
Li, CL
Bell, JR
Dubois, PJ
Moss, DJ
Good, MF
Kelso, A
Cohen, LK
Dranoff, G
Mulligan, RC
Title 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
Journal name Cancer Immunology Immunotherapy   Check publisher's open access policy
ISSN 0340-7004
Publication date 1997-03-01
Year available 1997
Sub-type Article (original research)
DOI 10.1007/s002620050349
Open Access Status Not yet assessed
Volume 44
Issue 1
Start page 10
End page 20
Total pages 11
Place of publication NEW YORK
Publisher SPRINGER VERLAG
Language eng
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.
Keyword GM-CSF-transduced autologous melanoma vaccine
cerebral metastases acute cerebral oedema
tumour-reactive cytotoxic T lymphocytes
eosinophilia
C-reactive protein
Delayed-Type Hypersensitivity
Cytotoxic T-Lymphocytes
Allograft-Rejection
Metastatic Melanoma
Mutator Phenotype
Peripheral-Blood
Gene-Transfer
Tumor-Cells
Eosinophils
Vaccine
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: ResearcherID Downloads - Archived
 
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