An anti-CD19 antibody coupled to a tetanus toxin peptide induces efficient Fas ligand (FasL)-mediated cytotoxicity of a transformed human B cell line by specific CD4+ T cells.

Résumé : Treatment of B cell lymphoma patients with MoAbs specific for the common B cell marker (CD20) has shown a good overall response rate, but the number of complete remissions is still very low. The use of MoAbs coupled to radioisotopes can improve the results, but induces undesirable myelodepression. As an alternative, we proposed to combine the specificity of MoAbs with the immunogenicity of T cell epitopes. We have previously shown that an anti-Ig lambda MoAb coupled to an MHC class II-restricted universal T cell epitope peptide P2 derived from tetanus toxin induces efficient lysis of a human B cell lymphoma by a specific CD4+ T cell line. Here we demonstrate that the antigen presentation properties of the MoAb peptide conjugate are maintained using a MoAb directed against a common B cell marker, CD19, which is known to be co-internalized with the B cell immunoglobulin receptor. In addition, we provide evidence that B cell lysis is mediated by the Fas apoptosis pathway, since Fas (CD95), but not tumour necrosis factor receptor (TNFr) or TNF-related receptors, is expressed by the target B cells, and FasL, but not perforin, is expressed by the effector T cells. These results show that B cell lymphomas can be 'foreignized' by MoAb-peptide P2 conjugates directed against the common B cell marker CD19 and eliminated by peptide P2-specific CD4+ T cells, via the ubiquitous Fas receptor. This approach, which bridges the specificity of passive antibody therapy with an active T cell immune response, may be complementary to and more efficient than the present therapy results with unconjugated chimeric anti-CD20 MoAbs.
Type de document :
Article dans une revue
Clinical and Experimental Immunology, Wiley, 1998, pp.173-8
Liste complète des métadonnées

https://hal-pasteur.archives-ouvertes.fr/pasteur-01402850
Contributeur : Bérengère Hugot <>
Soumis le : vendredi 25 novembre 2016 - 11:34:10
Dernière modification le : mercredi 7 décembre 2016 - 11:24:20

Identifiants

  • HAL Id : pasteur-01402850, version 1
  • PUBMED : 9822273

Collections

Citation

G Eberl, S Jiang, Z Yu, P Schneider, G Corradin, et al.. An anti-CD19 antibody coupled to a tetanus toxin peptide induces efficient Fas ligand (FasL)-mediated cytotoxicity of a transformed human B cell line by specific CD4+ T cells.. Clinical and Experimental Immunology, Wiley, 1998, pp.173-8. 〈pasteur-01402850〉

Partager

Métriques

Consultations de la notice

32