Treatment of post-transplant lymphomas with anti-B-cell monoclonal antibodies

Abstract

The treatment of post-transplant lymphomas still needs major improvements in order to put the patient in remission and to retain graft function. Chemotherapy is far too toxic in these patients. A more specific treatment such as anti-B-cell monoclonal antibody is very promising. The cytotoxic effect of antibody relies mainly on complement-induced and antibody-dependent cellular cytotoxicity; apoptosis may also induce tumor cell death. B-cell antigens expressed on the cell surface are the targets of antibody attack; some specificities may be chosen because of their level of expression or because of signaling induced within the cell. Anti-B-cell antibodies can be produced by genetic engineering in order to be humanized or to carry bispecific Fabs. The efficacy and safety of anti-B-cell monoclonal antibodies (mAbs) in transplant patients have been proven with different antibodies such as anti-CD21/CD24 mAb, anti-CD38 mAb and anti-CD20 mAb. In a retrospective analysis of different centers in France, rituximab (anti-CD20 mAb, Roche Products) achieved an overall 69% remission rate in 34 organ and bone-marrow transplant patients. But the conditions of use of antibody must be better defined, particularly with regard to the immunosuppressive therapy, the type of tumor and the dose of antibody. We must also improve our understanding of the in vivo mechanisms of action of antibody to develop more efficient antibody constructs.