Surface Levels of CD20 Determine Anti-CD20 Antibodies Mediated Cell Death In Vitro

Abstract

BackgroundThe sensitivity of human Burkitt's lymphoma cells to rituximab (Rtx) and tositumomab (Tst) was assessed on cells expressing different levels of CD20 on surface. Cells that harbor low CD20 levels may resists against therapeutics response to CD20-specific antibodies. We postulated that, radiation-induced modulation of CD20 surface levels may play a crucial and central role in determining the relative efficacy of rituximab and tositumomab in treating Burkitt's lymphoma disease. Here, we examined the γ-radiation-induced CD20 expression in the Burkitt lymphoma cell line ‘Daudi’ and the relation of differential levels of CD20 with anti-CD20 mAbs mediated cell death.MethodologyIn this study we examined kinetics of CD20 expression following sub lethal doses ofγ-radiation to Daudi cells and thereafter anti-CD20 mAbs (rituximab and tositumomab) were added in cell suspensions. The correlation of kinetics of CD20 expression and cells treated with anti-CD20 mAbs/or corresponding isotype Abs with special reference to changes in mitochondrial membrane potential and reactive oxygen species generation was also examined. Further, we also investigated the efficacy of anti-CD20 mAbs and possible induction of cell death in relation to levels of CD20 cell surface expression.ConclusionThis report provides evidence that CD20 expression can be induced by exposure of cells to γ-radiation. In addition, these findings demonstrated that the efficacy of anti-CD20 mAbs is dependent on the surface levels of CD20. Based on these findings, we hypothesized (i) irradiation just prior to immunotherapy may provide new treatment options even in aggressive B cell tumors, which are resistant to current therapies in vivo (ii) The efficacy of induction of apoptosis varies with type of monoclonal antibodies in vitro.

Epigenetic inhibitors sensitize DLBCL cells to rituximab and doxorubicin

“…Rituximab and doxorubicin were selected because they are the main contributors of R-CHOP. While the main mechanism of action of monoclonal antibodies is to reactivate the immune response, rituximab can also induce direct apoptosis ( 49, 50 ), making it suitable for this in vitro study.…”

The therapeutic effectiveness of 177Lu-lilotomab in B-cell non-Hodgkin lymphoma involves modulation of G2/M cell cycle arrest

“…Currently, most patients with B-cell NHL are treated with anti-CD20 monoclonal antibodies (mAb) (e.g., rituximab) and chemotherapy [1,2]. The response rate to rituximab alone is rather modest [3], and after treatment, some lymphomas become refractory to this therapy [4][5][6][7]. The 5-year overall survival rate is reduced in patients with follicular lymphoma (FL) who experience disease progression or relapse within 2 years after first-line immuno-chemotherapy compared with those without relapse [8,9].…”

Les anticorps monoclonaux anti-tumoraux

“…De même, alors que, dans un modèle de cancer colorectal, le traitement par l'anticorps anti-EGFR, le cétuximab, ou par une chimiothérapie ont peu d'impact sur la réponse immunitaire anti-tumorale suite à la mort de la cellule tumorale, leur combinaison thérapeutique déclenche une mort cellulaire immunogénique se traduisant par une phagocytose plus active et un recrutement de lymphocytes T spécifiques [33]. L'importance de l'association radiothérapie/anti-CD20 a également été montrée par une étude dans laquelle le traitement par radiothérapie de cellules de lymphomes augmente l'efficacité thérapeutique d'un AcM [34]. De telles combinaisons s'étendent désormais à de nombreux autres cancers.…”