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
✍ Scribed by Zhiwei Yu; Frank Healy; Danila Valmori; Patricia Escobar; Giampietro Corradin; Jean-Pierre Mach
- Publisher
- John Wiley and Sons
- Year
- 1994
- Tongue
- French
- Weight
- 729 KB
- Volume
- 56
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
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 antiidiotype 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 PZ (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 PZ coupled by an S-S bridge to monoclonal antibodies directed to the A light chain of human immunoglobulin, human B-lymphoma cells can be specifically lysed by a CD4 Tlymphocyte clone specific for the PZ peptide. Antibody without peptide did not induce B-cell killing by the CD4 T-lymphocyte clone. The free cystein-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. It is reasonable to expect that, in vivo, the anti-idiotype antibodies will selectively transport the tetanus toxin peptides to the Blymphoma cells, which will process the conjugates and present the peptides to the patients' CD4 T-cell repertoire. Our tetanus-toxoid-vaccinated population has T cells specific for the immunogenic peptide and these, in principle, could be further expanded prior to injection of the conjugate.