Durable complete clinical responses in a phase I/II trial using an autologous melanoma cell/dendritic cell vaccine

O'Rourke, Michael G. E., Johnson, Maree, Lanagan, Catherine, See, Janet, Yang, Jie, Bell, John R., Slater, Greg J., Kerr, Beverley M., Crowe, Beth, Purdie, David M., Elliott, Suzanne L., Ellem, Kay A. O. and Schmidt, Christopher W. (2003) Durable complete clinical responses in a phase I/II trial using an autologous melanoma cell/dendritic cell vaccine. Cancer Immunology Immunotherapy, 52 6: 387-395. doi:10.1007/s00262-003-0375-x


Author O'Rourke, Michael G. E.
Johnson, Maree
Lanagan, Catherine
See, Janet
Yang, Jie
Bell, John R.
Slater, Greg J.
Kerr, Beverley M.
Crowe, Beth
Purdie, David M.
Elliott, Suzanne L.
Ellem, Kay A. O.
Schmidt, Christopher W.
Title Durable complete clinical responses in a phase I/II trial using an autologous melanoma cell/dendritic cell vaccine
Journal name Cancer Immunology Immunotherapy   Check publisher's open access policy
ISSN 0340-7004
1432-0851
Publication date 2003
Sub-type Article (original research)
DOI 10.1007/s00262-003-0375-x
Volume 52
Issue 6
Start page 387
End page 395
Total pages 9
Editor E. Mihich
Place of publication Germany
Publisher Springer-Verlag
Collection year 2003
Language eng
Subject C1
320206 Tumor Immunology
730108 Cancer and related disorders
Abstract Advanced metastatic melanoma is incurable by standard treatments, but occasionally responds to immunotherapy. Recent trials using dendritic cells (DC) as a cellular adjuvant have concentrated on defined peptides as the source of antigens, and rely on foreign proteins as a source of help to generate a cell-mediated immune response. This approach limits patient accrual, because currently defined, non-mutated epitopes are restricted by a small number of human leucocyte antigens. It also fails to take advantage of mutated epitopes peculiar to the patient's own tumour, and of CD4(+) T lymphocytes as potential effectors of anti-tumour immunity. We therefore sought to determine whether a fully autologous DC vaccine is feasible, and of therapeutic benefit. Patients with American Joint Cancer Committee stage IV melanoma were treated with a fully autologous immunotherapy consisting of monocyte-derived DC, matured after culture with irradiated tumour cells. Of 19 patients enrolled into the trial, sufficient tumour was available to make treatments for 17. Of these, 12 received a complete priming phase of six cycles of either 0.9X10(6) or 5X10(6) DC/intradermal injection, at 2-weekly intervals. Where possible, treatment continued with the lower dose at 6-weekly intervals. The remaining five patients could not complete priming, due to progressive disease. Three of the 12 patients who completed priming have durable complete responses (average duration 3 5 months +), three had partial responses, and the remaining six had progressive disease (WHO criteria). Disease regression was not correlated with dose or with the development of delayed type hypersensitivity responses to intradermal challenge with irradiated, autologous tumour. However, plasma S-100B levels prior to the commencement of treatment correlated with objective clinical response (P = 0.05) and survival (log rank P < 0.001). The treatment had minimal side-effects and was well tolerated by all patients. Mature, monocyte-derived DC preparations exposed to appropriate tumour antigen sources can be reliably produced for patients with advanced metastatic melanoma, and in a subset of those patients with lower volume disease their repeated administration results in durable complete responses.
Keyword Oncology
Immunology
Dendritic Cells
Melanoma
Immunotherapy
Cytotoxic T Lymphocytes
S-100b
Human Dendritic Cells
Cytotoxic T-cells
Metastatic Melanoma
Cancer-immunotherapy
Malignant-melanoma
Human Blood
Tumor
Mature
Immune
Serum
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2004 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Wed, 15 Aug 2007, 02:46:18 EST