Purpose: AME-133v is a humanized monoclonal antibody engineered to have increased affinity to CD20 and mediate antibody-dependent cell-mediated cytotoxicity (ADCC) better than rituximab. Safety, pharmacokinetics, and efficacy were assessed in a phase 1/2 trial in patients with previously treated follicular lymphoma (FL).
Patients And Methods: AME-133v was characterized in vitro by ADCC and cell binding assays. A phase 1 study was conducted in which 23 previously treated patients with FL were assigned sequentially to one of five dose-escalation cohorts of AME-133v at 2, 7.5, 30, 100, or 375 mg/m(2) weekly × 4 doses.
Results: AME-133v showed a 13- to 20-fold greater binding affinity for CD20 and was 5- to 7-fold more potent than rituximab in ADCC assays. Cell binding assays showed AME-133v and rituximab competed for an overlapping epitope on the CD20 antigen, and AME-133v inhibited binding of biotinylated rituximab to CD20 in a concentration-dependent manner. AME-133v was well tolerated by patients and common related adverse events included chills and fatigue. One patient experienced a dose-limiting toxicity of neutropenia. AME-133v showed nonlinear pharmocokinetics with properties similar to rituximab. Selective reduction of B cells during and after AME-133v treatment was shown by flow cytometry of peripheral blood. A partial or complete response was observed in 5 of 23 (22%) patients and the median progression-free survival was 25.4 weeks.
Conclusions: AME-133v was safe and well tolerated at the doses tested. AME-133v showed encouraging results as an anti-CD20 therapy in heavily pretreated FL patients with the less favorable FcγRIIIa F-carrier genotype.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1158/1078-0432.CCR-11-0850 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Immunotherapy in indolent Non-Hodgkin's Lymphoma.
Leuk Res Rep
May 2022
Division of hematology-oncology, American University of Beirut Medical Center, Beirut, Lebanon.
Article Synopsis
- - The treatment options for non-Hodgkin lymphoma (NHL) have improved with the introduction of monoclonal antibody (MAB) therapy, particularly focusing on B cell and T cell subtypes, and categorized into aggressive and indolent forms.
- - Rituximab, an anti-CD20 MAB, revolutionized treatment for indolent B cell NHL, like follicular lymphoma, by directly targeting cancerous B cells and becoming FDA approved in 1997.
- - Despite its effectiveness, challenges such as resistance mechanisms have prompted interest in combining immunotherapy with radio-sensitizing agents, leading to advancements in drugs like 90Y-ibritumomab tiuxetan and ofatumumab
Epitope Mapping of Rituximab Using HisMAP Method.
Monoclon Antib Immunodiagn Immunother
February 2022
Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Sendai, Japan.
CD20 is expressed in the B lymphocyte, and an effective target for the detection and treatment of B cell lymphomas. Therefore, CD20 has been studied as a therapeutic target of B cell lymphomas and autoimmune disorders. Specific anti-CD20 monoclonal antibodies (mAbs), such as rituximab, ofatumumab, veltuzumab, and ocaratuzumab, have been developed.
View Article and Find Full Text PDFCellular Cytotoxicity of Next-Generation CD20 Monoclonal Antibodies.
Cancer Immunol Res
October 2018
Division of Hematology/Oncology, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York.
CD20 monoclonal antibodies (CD20 mAb) induce cellular cytotoxicity, which is traditionally measured by antibody-dependent cellular cytotoxicity (ADCC) assays. However, data suggest that antibody-dependent cellular phagocytosis (ADCP) is the primary cytotoxic mechanism. We directly compared ADCP versus ADCC using primary human cells.
View Article and Find Full Text PDFDancing partners at the ball: Rational selection of next generation anti-CD20 antibodies for combination therapy of chronic lymphocytic leukemia in the novel agents era.
Blood Rev
September 2017
Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia; Victorian Comprehensive Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia; Faculty of Medicine, University of Melbourne, Building 181, Grattan Street, Parkville, VIC 3052, Australia. Electronic address:
The anti-CD20 antibodies represent a major advancement in the therapeutic options available for chronic lymphocytic leukemia. The addition of rituximab, ofatumumab and obinutuzumab to various chemotherapy regimens has led to considerable improvements in both response and survival. Ocaratuzumab, veltuzumab and ublituximab are currently being explored within the trial setting.
View Article and Find Full Text PDFFuture therapies for pemphigus vulgaris: Rituximab and beyond.
J Am Acad Dermatol
April 2016
Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York.
The conventional treatment for patients with pemphigus vulgaris (PV) centers on global immunosuppression, such as the use of steroids and other immunosuppressive drugs, to decrease titers of antidesmoglein autoantibodies responsible for the acantholytic blisters. Global immunosuppressants, however, cause serious side effects. The emergence of anti-CD20 biologic medications, such as rituximab, as an adjunct to conventional therapy has shifted the focus to targeted destruction of autoimmune B cells.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!