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(-CELLS() T)

Treatment of B cell lymphoma patients with MoAbs specific for the comm on B cell marker (CD20) has shown a good overall response rate, but th e number of complete remissions is still very low. The use of MoAbs co upled to radioisotopes can improve the results, but induces undesirabl e myelodepression. As an alternative, we proposed to combine the speci ficity of MoAbs with the immunogenicity of T cell epitopes. We have pr eviously shown that an anti-Ig lambda MoAb coupled to an MHC class II- restricted universal T cell epitope peptide P2 derived from tetanus to xin induces efficient lysis of a human B cell lymphoma by a specific C D4(+) T cell line. Here we demonstrate that the antigen presentation p roperties of the MoAb-peptide conjugate are maintained using a MoAb di rected against a common B cell marker, CD19, which is known to be co-i nternalized with the B cell immunoglobulin receptor. In addition, we p rovide evidence that B cell lysis is mediated by the Fas apoptosis pat hway, since Fas (CD95), but not tumour necrosis factor receptor (TNFr) or TNF-related receptors, is expressed by the target B cells, and Fas t, but not perforin, is expressed by the effector T cells. These resul ts show that B cell lymphomas can be 'foreignized' by MoAb-peptide P2 conjugates directed against the common B cell marker CD19 and eliminat ed by peptide P2-specific CD4(+) T cells, via the ubiquitous Fas recep tor. 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.