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Human Anti-Idiotypic Antibodies Induced a Humoral and Cellular Immune Response Against a Colorectal Carcinoma-Associated Antigen in Patients

Jan Fagerberg, Michael Steinitz, Hans Wigzell, Per Askelof and Hakan Mellstedt
Proceedings of the National Academy of Sciences of the United States of America
Vol. 92, No. 11 (May 23, 1995), pp. 4773-4777
Stable URL: http://www.jstor.org/stable/2367612
Page Count: 5
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Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Human Anti-Idiotypic Antibodies Induced a Humoral and Cellular Immune Response Against a Colorectal Carcinoma-Associated Antigen in Patients
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Abstract

Induction of immunity against antigens expressed on tumor cells might prevent or delay recurrence of the disease. Six patients operated on for colorectal carcinoma were immunized with human monoclonal anti-idiotypic antibodies (h-Ab2) against the mouse 17-1A anti-colon carcinoma antibody, mimicking a nominal antigen (GA733-2). All patients developed a long-lasting T-cell immunity against the extracellular domain of GA733-2 (GA733-2E) (produced in a baculovirus system) and h-Ab2. This was shown in vitro by specific cell proliferation (DNA-synthesis) assay as well as by interleukin 2 and interferon γ production and in vivo by the delayed-type hypersensitivity reaction. Five patients mounted a specific humoral response (IgG) against the tumor antigen GA733-2E (ELISA) and tumor cells expressing GA733-2. Epitope mapping using 23 overlapping peptides of GA733-2E revealed that the B-cell epitope was localized close to the N terminus of GA733-2. Binding of the antibodies to the tumor antigen and to one 18-aa peptide was inhibited by h-Ab2, indicating that the antibodies were able to bind to the antigen as well as to h-Ab2. The results suggest that our h-Ab2 might be able to induce an anti-tumor immunity which may control the growth of tumor cells in vivo.

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