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.