Send to

Choose Destination
Methods Mol Biol. 2011;731:407-19. doi: 10.1007/978-1-61779-080-5_33.

Development of rituximab-resistant B-NHL clones: an in vitro model for studying tumor resistance to monoclonal antibody-mediated immunotherapy.

Author information

Department of Surgery, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.


Therapeutic strategies for cancer include chemotherapy, immunotherapy, and radiation. Such therapies result in significant short-term clinical responses; however, relapses and recurrences occur with no treatments. Targeted therapies using monoclonal antibodies have improved responses with minimal toxicities. For instance, Rituximab (chimeric anti-CD20 monoclonal antibody) was the first FDA-approved monoclonal antibody for the treatment of patients with non-Hodgkin's lymphoma (NHL). The clinical response was significantly improved when used in combination with chemotherapy. However, a subset of patients does not respond or becomes resistant to further treatment. Rituximab-resistant (RR) clones were used as a model to address the potential mechanisms of resistance. In this chapter, we discuss the underlying molecular mechanisms by which rituximab signals the cells and modifies several intracellular survival/antiapoptotic pathways, leading to its chemo/immunosensitizing activities. RR clones were developed to mimic in vivo resistance observed in patients. In comparison with the sensitive parental cells, the RR clones are refractory to rituximab-mediated cell signaling and chemosensitization. Noteworthy, interference with the hyperactivated survival/antiapoptotic pathways in the RR clones with various pharmacological inhibitors mimicked rituximab effects in the parental cells. The development of RR clones provides a paradigm for studying resistance by other anticancer monoclonal antibodies in various tumor models.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center