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

被引:80
作者
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
机构
[1] QUEENSLAND INST MED RES,BANCROFT CTR,EPSTEIN BARR VIRUS UNIT,BRISBANE,QLD 4029,AUSTRALIA
[2] QUEENSLAND INST MED RES,BANCROFT CTR,MALARIA & ARBOVIRUS UNIT,BRISBANE,QLD 4029,AUSTRALIA
[3] QUEENSLAND INST MED RES,BANCROFT CTR,TRANSPLANTAT BIOL UNIT,BRISBANE,QLD 4029,AUSTRALIA
[4] QUEENSLAND INST MED RES,BANCROFT CTR,QUEENSLAND DAIKYO RES UNIT,LEUKAEMIA FDN,BRISBANE,QLD 4029,AUSTRALIA
[5] MATER ADULT PUBL HOSP,DEPT SURG,BRISBANE,QLD,AUSTRALIA
[6] MATER ADULT PUBL HOSP,DEPT PATHOL,BRISBANE,QLD,AUSTRALIA
[7] MATER PRIVATE HOSP,MRI UNIT,BRISBANE,QLD,AUSTRALIA
[8] SOMATIX THERAPY CORP,ALAMEDA,CA
[9] HARVARD UNIV,SCH MED,BOSTON,MA
[10] DANA FARBER CANC INST,BOSTON,MA 02115
[11] WHITEHEAD INST,CAMBRIDGE,MA 02142
[12] MIT,DEPT BIOL,CAMBRIDGE,MA 02142
关键词
GM-CSF-transduced autologous melanoma vaccine; cerebral metastases acute cerebral oedema; tumour-reactive cytotoxic T lymphocytes; eosinophilia; C-reactive protein;
D O I
10.1007/s002620050349
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
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页码:10 / 20
页数:11
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