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International Journal of Colorectal Disease
Published in: International Journal of Colorectal Disease 5/2005

01-09-2005 | Original Article

Immune responses in advanced colorectal cancer following repeated intradermal vaccination with the anti-CEA murine monoclonal antibody, PR1A3: results of a phase I study

Authors: A. P. Zbar, H. Thomas, R. W. Wilkinson, M. Wadhwa, K. N. Syrigos, E. L. Ross, P. Dilger, T. G. Allen-Mersh, W. A. Kmiot, A. A. Epenetos, D. Snary, W. F. Bodmer

Published in: International Journal of Colorectal Disease | Issue 5/2005

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Abstract

Background and aims

The aim was to determine the toxicity, clinical and immune responses to the murine monoclonal anti-carcinoembryonic antigen (CEA) antibody, PR1A3, in patients with advanced colorectal cancer.

Materials and methods

Fifteen patients with advanced colorectal cancer received either 0.5-, 1.0- or 5.0-mg doses of PR1A3 mixed with 10% w/v Alum adjuvant (Superfos Biosector, Denmark) intradermally at 4-week intervals for 3 months. Patient serum was assessed for anti-idiotypic (Ab2), anti-anti-idiotypic (Ab3) and human anti-mouse antibody (HAMA) reactivity. Peripheral blood mononuclear cell (PBMC) proliferation with phytohaemagglutinin (PHA), CEA and PR1A3, stimulated IL-2, IL-4 and IFN-γ levels and PR1A3-stimulated IL-2 receptor expression during immunotherapy were determined. Comparisons were made with 16 age-matched controls without malignant disease.

Results

Hyperimmune sera from 12 of the 15 patients showed Ab2 reactivity with no detectable Ab3 responses. Strong HAMA reactivity was recorded in 7 of the 15 cases with no adverse clinical effect. Delayed-type hypersensitivity (DTH) responses developed in 12 of the 15 patients. Pre-treatment PBMC proliferation with PHA was subnormal in each patient compared with controls, becoming normal (or supranormal) in all patients during immunisation (P<0.001). PBMC proliferation with CEA and PR1A3 increased during immunotherapy (P<0.001) along with stimulated production of IL-2, IFN-γ and IL-2 receptor expression. Progressive disease was observed in 14 of the 15 patients with minimal toxicity.

Conclusion

PR1A3 generated limited idiotypic responses but robust DTH reactivity in most patients. In vitro PBMC proliferation with mitogens and recall antigens is greatly increased during the course of immunisation, with a shift in stimulated cytokine profile.
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Metadata
Title
Immune responses in advanced colorectal cancer following repeated intradermal vaccination with the anti-CEA murine monoclonal antibody, PR1A3: results of a phase I study
Authors
A. P. Zbar
H. Thomas
R. W. Wilkinson
M. Wadhwa
K. N. Syrigos
E. L. Ross
P. Dilger
T. G. Allen-Mersh
W. A. Kmiot
A. A. Epenetos
D. Snary
W. F. Bodmer
Publication date
01-09-2005
Publisher
Springer-Verlag
Published in
International Journal of Colorectal Disease / Issue 5/2005
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI
https://doi.org/10.1007/s00384-004-0726-x

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