In vitro: Complement-dependent cytotoxicity(CDC), complement-dependent cellular cytotoxicity(CDCC), antibody-dependent cytotoxicity (ADCC) as well as the induction of apoptosis have been claimed to be responsible for the efficacy of rituximab. Rituximab can induce death of malignant B cell lines in vitro. Th strength of this effect varies considerably between target cell lines. Changes that have been identified in response to rituximab in vitro include inhibition of p38 mitogen-activated protein kinase, NF-κB, extracellular signal-regulated kinase 1/2 (ERK 1/2) and AKT antiapoptotic survival pathways. Rituximab is highly efficient at mediating CMC(complement dependent cytotoxicity) of various B cell lines as well as fresh malignant B cell samples. CD20-binding capacity of rituximab is dose-dependentv.
In vivo: A number of in vivo tumor models suggest the anti-tumor activity of rituximab is dependent, at least in part, on complement. Rituximab can deplete B cells for several months and, as such, could represent an effective therapy for B cell-mediated autoimmune diseases. Rituximab is now widely used in onco-haematology and is currently in development in several autoimmune diseases.
|Cell lines||Two CD20-positive follicular lymphoma cell lines (DOHH-2, WSU-NHL) and one CD20-positive Burkitt's lymphoma cell line (Raji)|
|Preparation method||Samples of 1×10^6 cells/mL medium are incubated with rituximab and the various cytotoxic drugs for 24 and 48 hours.|
|Incubation time||24 and 48 hours|
|Animal models||SCID mice|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
Rituximab for indolent lymphomas before and after allogeneic hematopoietic stem cell transplantation.
Cieri N, et al. Curr Opin Hematol. 2015 Nov;22(6):469-75. PMID: 26390162.
The role of rituximab in adults with warm antibody autoimmune hemolytic anemia.
Dierickx D, et al. Blood. 2015 May 21;125(21):3223-9. PMID: 25827833.
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