Development of Rituximab-Resistant Lymphoma Clones with Altered Cell Signaling and Cross-Resistance to Chemotherapy

Abstract

Immunotherapy with rituximab (chimeric anti-CD20 monoclonal antibody, Rituxan

Immunotherapy of recurrent B-cell malignancies after allo-SCT with Bi20 (FBTA05), a trifunctional anti-CD3 × anti-CD20 antibody and donor lymphocyte infusion

“…Lymphoma cells may become resistant by decreased expression of CD20 antigen, or they may also activate antiapoptotic signal transduction pathways, which Immunotherapy of NHL with Bi20 and DLI R Buhmann et al renders these cells resistant to chemotherapy. 19,20 Host factors involve effector cells of antibody-dependent cellular cytotoxicity and the reticulo-endothelial system removing antibody-loaded cells. 18 These functions may be defective;…”

Caspase-2 Triggers Bax-Bak-dependent and -independent Cell Death in Colon Cancer Cells Treated with Resveratrol

“…However, they can be used as potent agents to bypass drug resistance along with other antitumor agents that primarily act through classical apoptosis. A study in this line suggests that resveratrol is an ideal candidate agent to enhance the apoptotic potential of antitumor agents like TRAIL and paclitaxel (55,56). More preclinical studies are needed to clarify whether 50 M concentration required for the desired biological effect can be achieved in vivo.…”

Understanding and circumventing resistance to anticancer monoclonal antibodies

“…46 Several studies have shown that resistant cells display constitutive hyperactivation of the survival pathways NFκB and ERK1/2, leading to overexpression of Bcl-2, Bcl-2-related gene and Mcl-1. 8 In the in vivo resistant RL model, Bcl-X L was also found more highly expressed in rituximab-resistant cells. 28 This confirms the recent results obtained in vitro by Jazirehi et al 8 showing that the phenotype of resistant cells to rituximab may be associated with a higher expression of Bcl-X L .…”

“…8 In the in vivo resistant RL model, Bcl-X L was also found more highly expressed in rituximab-resistant cells. 28 This confirms the recent results obtained in vitro by Jazirehi et al 8 showing that the phenotype of resistant cells to rituximab may be associated with a higher expression of Bcl-X L . Moreover, we found an overexpression of YY1, a negative regulator of Fas and Trail receptor DR5 expression, that can inhibit apoptosis.…”

“…Induction of apoptosis by rituximab alone has been reported in the absence of accessory cells, but has mostly been described using cell lines derived from patients with Burkitt lymphoma, a subtype of NHL for which the clinical indication of rituximab has not yet been as well documented. 8,9 Conversely rituximab has been shown by several groups to possess activity in murine models of xenotransplanted human CD20 positive lymphoma lines. Notwithstanding the limitations due to the use of immunocompromised mice, these models have been very informative in determining the contribution of CDC or ADCC in vivo, and offer the possibility of analyzing signaling pathways in tumors.…”