Rituximab (monoclonal anti-CD20 antibody): mechanisms of action and resistance

Smith, Mitchell R.

doi:10.1038/sj.onc.1206939

Cited by 692 publications

(551 citation statements)

References 68 publications

Supporting

Mentioning

522

Contrasting

Unclassified

Order By: Relevance

“…Rituximab acts by binding CD201 B cells. Toxicity and efficacy are related to events after binding, which include B cell signaling, complement activation, direct apoptosis, and antibody dependent cellular cytotoxicity [13]. Complement activation and cytokine secretion, in particular, seems to be the causative factors in side effects associated with infusion reactions [14].…”

Section: Discussionmentioning

confidence: 99%

Rituximab‐induced interstitial lung disease

2007

View full text Add to dashboard Cite

The aim of this study is to characterize rituximab‐induced interstitial lung disease (R‐ILD). The information on all reported cases of R‐ILD was reviewed. This analysis focused on patient characteristics, underlying disease, rituximab dosing schedule, and R‐ILD characteristic‐like symptoms, diagnosis, treatment, and outcomes. Sixteen cases of R‐ILD, including our two cases, have been reported in the literature. Commonalities include older age, clinical presentation, computerized tomography findings, pulmonary function tests, and biopsy findings. Therapy included corticosteroids and broad spectrum antibiotics. Prognosis has been variable. Patients who worsen despite corticosteroids have a poor outcome. The pathogenesis of R‐ILD is largely unknown. Potential explanations for R‐ILD may include the induction and release of cytotoxic substances. R‐ILD is a rare but potentially fatal pulmonary toxicity due to rituximab. R‐ILD should be considered in patients who present with dyspnea, fever, and cough, and there is no clear evidence of infection. Prompt diagnosis and treatment with corticosteroids is essential. Am. J. Hematol. 82:916–919, 2007. © 2007 Wiley‐Liss, Inc.

show abstract

Section: Discussionmentioning

confidence: 99%

Rituximab‐induced interstitial lung disease

2007

View full text Add to dashboard Cite

show abstract

“…Recently, several mAbs that predominantly act by ADCC and CDC have been approved for the treatment of cancer patients. These include chimaeric IgG1 mAb rituximab (Rituxan s ) binding to the B-cell differentiation antigen CD20 for the treatment of Bcell lymphomas (Grillo-Lopez et al, 1999;Smith, 2003), humanised IgG1 mAb trastuzumab (Herceptin s ) targeting HER-2 (human epithelial growth factor receptor type 2) overexpressed in a subgroup of breast cancers (Vogel et al, 2001), humanised IgG1 alemtuzumab (Campath s ) targeting the differentiation antigen CD52 for the treatment of B-cell chronic lymphocytic leukaemia (Hale et al, 1998;Kottaridis et al, 2000;Faulkner et al, 2004) and edrecolomab (Panorex s ), a murine IgG2a mAb targeting Ep-CAM (epithelial cell adhesion molecule), which gained temporary approval in Germany for the treatment of colorectal carcinoma (Riethmuller et al, 1994;Gruber et al, 1996;Schwartzberg, 2001;White et al, 2001). Several other mAbs are currently at advanced stages of clinical development.…”

mentioning

confidence: 99%

Cellular and complement-dependent cytotoxicity of Ep-CAM-specific monoclonal antibody MT201 against breast cancer cell lines

Prang¹,

Preithner²,

Brischwein³

et al. 2005

Br J Cancer

130

View full text Add to dashboard Cite

MT201 is a fully human monoclonal IgG1 antibody with moderate affinity for epithelial cell adhesion molecule (Ep-CAM) being clinically developed for the treatment of carcinomas. Like many other clinically validated IgG1 monoclonal antibodies, MT201 primarily acts by antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Here, we analysed ADCC and CDC induced by MT201 and, as reference, trastuzumab against a panel of nine human breast cancer cell lines expressing distinct surface levels of Ep-CAM and human epithelial growth factor receptor type 2 antigen. Maximal cell lysis by ADCC by MT201 and trastuzumab in the presence of peripheral mononuclear cells did not significantly differ when averaged over the nine cell lines, but showed marked differences with respect to individual cell lines. The extent of cell lysis at intermediate surface target density was highly variable, suggesting a dominant influence of other susceptibility factors. Only one breast cancer cell line was eliminated via CDC, but only by MT201. Resistance to CDC appeared to correlate with high expression levels of complement resistance factors. Our present data as well as recent data on the prevalence and prognostic relevance of Ep-CAM expression in metastatic breast cancer suggest that Ep-CAM-specific monoclonal IgG1 antibodies may have a significant therapeutic potential in the treatment of breast cancer.

show abstract

“…Rituximab acts primarily by stimulating antibody-dependent as well as complementdependent cytotoxicity. 16,17 Fludarabine is capable of down-regulating the complement inhibitor CD55, which is partially responsible for the decreased activity of rituximab in therapy-resistant NHL. Thus, fludarabine and rituximab exert synergistic effects, leading to increased response rates.…”

Section: Mechanism Of Actionmentioning

confidence: 99%