Article: article from journal or magazin.
Peptide-antibody conjugates for tumour therapy: a MHC-class-II-restricted tetanus toxin peptide coupled to an anti-Ig light chain antibody can induce cytotoxic lysis of a human B-cell lymphoma by specific CD4 T cells.
International Journal of Cancer
Anti-idiotype antibody therapy of B-cell lymphomas, despite numerous promising experimental and clinical studies, has so far met with limited success. Tailor-made monoclonal anti-idiotype antibodies have been injected into a large series of lymphoma patients, with a few impressive complete tumour remissions but a large majority of negative responses. The results presented here suggest that, by coupling to antilymphoma idiotype antibodies a few molecules of the tetanus toxin universal epitope peptide P2 (830-843), one could markedly increase the efficiency of this therapy. We show that after 2-hr incubation with conjugates consisting of the tetanus toxin peptide P2 coupled by an S-S bridge to monoclonal antibodies directed to the lambda light chain of human immunoglobulin, human B-lymphoma cells can be specifically lysed by a CD4 T-lymphocyte clone specific for the P2 peptide. Antibody without peptide did not induce B-cell killing by the CD4 T-lymphocyte clone. The free cysteine-peptide was also able to induce lysis of the B-lymphoma target by the T-lymphocyte clone, but at a molar concentration 500 to 1000 times higher than that of the coupled peptide. Proliferation assays confirmed that the antibody-peptide conjugate was antigenically active at a much lower concentration than the free peptide. They also showed that antibody-peptide conjugates required an intact processing function of the B cell for peptide presentation, which could be selectively inhibited by leupeptin and chloroquine.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid Sequence, Animals, Antibodies, Anti-Idiotypic/immunology, Antibodies, Anti-Idiotypic/therapeutic use, Antibodies, Monoclonal/immunology, Antibodies, Monoclonal/therapeutic use, CD4-Positive T-Lymphocytes/drug effects, CD4-Positive T-Lymphocytes/immunology, Chloroquine/pharmacology, Histocompatibility Antigens Class II/immunology, Histocompatibility Antigens Class II/therapeutic use, Humans, Immunoglobulin Light Chains/immunology, Immunoglobulin Light Chains/therapeutic use, Immunotoxins/metabolism, Immunotoxins/therapeutic use, Leupeptins/pharmacology, Lymphoma, B-Cell/drug therapy, Lymphoma, B-Cell/immunology, Mice, Mice, Inbred BALB C, Molecular Sequence Data, Peptides/therapeutic use, Tetanus Toxin/therapeutic use
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