Immunopathology and immunotherapy of lymphoblastic leukaemia

Abstract

Acute lymphoblastic leukaemia (ALL) rises from lymphoid progenitors. ALL cells show vast antigens linked to normal B-cell development and may be used as targets for immunotherapy. Since CD20 is expressed in B-ALL cells, rituximab, an anti-CD20 antibody used in B-cell non-Hodgkin’s lymphomas (B-NHLs), has also been used in the ALL. Reports have shown that the addition of CD20 antibodies to conventional chemotherapy leads to a higher rate of complete response as well as a better overall survival. CD22 molecule expression is found in more than 90 % of B-lineage ALL and is highly attractive for toxin-linked antibodies. Inotuzumab ozogamicin, an anti-CD22 antibody linked to calicheamicin, has shown high activity in phase II trials. CD19 is expressed in nearly all B-ALLs. Blinatumomab is a structured monoclonal antibody combining two single-chain antibodies to CD19 B cells and to CD3 T cells. It has shown encouraging results in the treatment of ALL. More recently, cell-based, especially T-cell-based, strategies have gained clinical interest, due to the curative effect of allogeneic stem cell transplantation, which is still the most effective immunotherapy for ALL and is mediated by donor T cells as “graft-versus-leukaemia (GVL)” effect; nonetheless, it also causes graft-versus-host disease (GVHD). The most promising approach is to target chimeric antigen receptors (CARs). CARs are composed of a single-chain variable-fragment (scFv) antibody specific to tumour antigen, fused to a transmembrane domain and a T-cell signalling moiety, most commonly either the CD3-ζ or Fc receptor γ cytoplasmic signalling domains. By choosing CD19 as the immunological target, primary clinical studies have shown high activity in ALL patients.