Rituximab

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Rituximab
Therapeutic monoclonal antibody
Source	Chimeric/human
Target	CD20
Identifiers
CAS number	174722-31-7
ATC code	L01XC02
DrugBank	BTD00014
Chemical data
Formula	C6416H9874N1688O1987S44
Mol. mass	143859.7 g/mol
Pharmacokinetic data
Bioavailability	?
Metabolism	?
Half life	?
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status
Routes	?

Rituximab, sold under the trade names Rituxan® and MabThera®, is a chimeric monoclonal antibody used in the treatment of B cell non-Hodgkin's lymphoma, B cell leukemia, and some autoimmune disorders.

Contents 1 History 2 Mechanism 3 Non-cancer use 4 Adverse events 5 Transplant use 6 References 7 External link 8 References

[edit] History

Rituximab was developed by IDEC Pharmaceuticals and initially approved by the FDA in 1997 for lymphoma that was refractory to other chemotherapy regimens. The original approval followed the availability of the McLaughlin et al^[1] study data. It now is standard therapy in the initial treatment of aggressive lymphomas (e.g. diffuse large B cell lymphoma) in combination with CHOP chemotherapy. It is currently co-marketed by Biogen Idec and Genentech in the U.S. market and Roche in the EU.

[edit] Mechanism

The antibody binds to the cluster of differentiation 20 (CD20). CD20 is widely expressed on B-cells, it does not shed, modulate or internalise. Although the function of CD20 is relatively unknown it has been indicated that CD20 could play a role in Ca2+ influx across plasma membranes, maintaining intracellular Ca2+ concentration and allowing activation of B cells. Also, apart from the Fc portion-mediated antibody-dependent cellular cytotoxicity (ADCC) and complement-mediated cytotoxicity (CDC); the exact mode of action of rituximab is unclear, but it has been found to have a general regulatory effect on the cell cycle, and to increase MHC II and adhesion molecules LFA-1 and LFA-3 (lymphocyte function-associated antigen), elicit shedding of CD23, down regulate the B-cell receptor, and induce apoptosis.

The combined effect results in the elimination of B cells (including the cancerous ones) from the body, allowing a new population of healthy B cells to develop from lymphoid stem cells.

Binder et al further described the part of the CD20 molecule that rituximab binds to: it turned out to be amino acids 170-173 and 182-185, which are physically close to each other as a result of a disulfide bond between amino acids 167 and 183.^[2]

[edit] Non-cancer use

Rituximab has been shown to be effective in rheumatoid arthritis in three randomised controlled trials and is now licensed for use in refractory rheumatoid disease.^[3] (FDA-approved for use in combination with methotrexate (MTX) for reducing signs and symptoms in adult patients with moderately- to severely-active rheumatoid arthritis (RA) who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies.) There is evidence for efficacy in a range of other autoimmune diseases, including immune thrombocytopenic purpura (ITP),^[4]vasculitis, bullous skin disorders, Sjogren's syndrome, and systemic lupus erythematosus.^{[citation needed]}

[edit] Adverse events

• Infections (from the package insert)
  • Hepatitis B reactivation
  • Other Viral Infections
  • Progressive Multifocal Leukoencephalopathy (PML))
• Immune toxicity, with depletion of B-cells in 70% to 80% of patients with non-Hodgkins lymphoma
• Pulmonary toxicity^[5]

[edit] Transplant use

Rituximab is now being used in the management of Renal Transplant recipients. This drug is especially useful in transplants involving incompatible blood groups. It is also used as induction therapy in highly sensitized patients going for renal transplantation.

[edit] References

1. ^ McLaughlin P, Grillo-Lopez AJ, Link BK, Levy R, Czuczman MS, Williams ME, Heyman MR, Bence-Bruckler I, White CA, Cabanillas F, Jain V, Ho AD, Lister J, Wey K, Shen D, Dallaire BK. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol 1998;16:2825-33. PMID 9704735.
2. ^ Binder M, Otto F, Mertelsmann R, Veelken H, Trepel M. (2006). "The epitope recognized by rituximab.". Blood 108: 1975-1978. PMID 16705086. 
3. ^ Edwards J, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close D, Stevens R, Shaw T (2004). "Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis.". N Engl J Med 350 (25): 2572-81. PMID 15201414. 
4. ^ Braendstrup P, Bjerrum OW, Nielsen OJ, Jensen BA, Clausen NT, Hansen PB, Andersen I, Schmidt K, Andersen TM, Peterslund NA, Birgens HS, Plesner T, Pedersen BB, Hasselbalch HC. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adult refractory idiopathic thrombocytopenic purpura. Am J Hematol 2005;78:275-80. PMID 15795920.
5. ^ Burton C, Kaczmarski R, Jan-Mohamed R (2003). "Interstitial pneumonitis related to rituximab therapy". N Engl J Med 348 (26): 2690-1; discussion 2690-1. PMID 12826649. 

[edit] External link

• Mabthera.com
• [1]

[edit] References

1. ^ McLaughlin P, Grillo-Lopez AJ, Link BK, Levy R, Czuczman MS, Williams ME, Heyman MR, Bence-Bruckler I, White CA, Cabanillas F, Jain V, Ho AD, Lister J, Wey K, Shen D, Dallaire BK. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol 1998;16:2825-33. PMID 9704735.
2. ^ Binder M, Otto F, Mertelsmann R, Veelken H, Trepel M. (2006). "The epitope recognized by rituximab.". Blood 108: 1975-1978. PMID 16705086. 
3. ^ Edwards J, Szczepanski L, Szechinski J, Filipowicz-Sosnowska A, Emery P, Close D, Stevens R, Shaw T (2004). "Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis.". N Engl J Med 350 (25): 2572-81. PMID 15201414. 
4. ^ Braendstrup P, Bjerrum OW, Nielsen OJ, Jensen BA, Clausen NT, Hansen PB, Andersen I, Schmidt K, Andersen TM, Peterslund NA, Birgens HS, Plesner T, Pedersen BB, Hasselbalch HC. Rituximab chimeric anti-CD20 monoclonal antibody treatment for adult refractory idiopathic thrombocytopenic purpura. Am J Hematol 2005;78:275-80. PMID 15795920.
5. ^ Burton C, Kaczmarski R, Jan-Mohamed R (2003). "Interstitial pneumonitis related to rituximab therapy". N Engl J Med 348 (26): 2690-1; discussion 2690-1. PMID 12826649. 

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