Trogocytosis of multiple B-cell surface markers by CD22 targeting with epratuzumab

Rossi, Edmund A.; Goldenberg, David M.; Michel, Rosana B.; Rossi, Diane L.; Wallace, Daniel J.; Chang, Chien-Hsing

doi:10.1182/blood-2012-12-473744

Cited by 98 publications

(91 citation statements)

References 51 publications

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“…Many of our findings of trogocytosis and effector function exhaustion with respect to CD20 mAbs in CLL have been replicated and extended, in some cases to other mAb-antigen pairs, in the clinic and in the laboratory Jones et al, 2012;Masuda et al, 2013;Rossi et al, 2013;Baig et al, 2014). Therefore, the implications of these studies with respect to use of CD20 mAbs may also pertain to other mAbs currently used to treat cancer.…”

Section: Possible Generalization To Othermentioning

confidence: 83%

“…During trogocytosis the mAb-opsonized target donor cell and the acceptor cell first form an immunologic synapse, due to binding of Fcg receptors on the acceptor cells to cognate Fc sites on the "immune-complexed" mAb bound to CD20 on the opsonized B cells (Joly and Hudrisier, 2003;Rossi et al, 2013;Taylor, 2013). The acceptor cell then removes the mAb/CD20 immune complex from the opsonized B cell along with a portion of the plasma membrane, and ultimately internalizes the immune complex.…”

Section: Trogocytosis Of Mab-opsonized Cellsmentioning

confidence: 99%

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Analyses of CD20 Monoclonal Antibody–Mediated Tumor Cell Killing Mechanisms: Rational Design of Dosing Strategies

Taylor

Lindorfer

2014

Mol Pharmacol

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Since approval of rituximab for treatment of B cell non-Hodgkin lymphoma, development of monoclonal antibodies (mAbs) for cancer treatment and elucidation of their cytotoxic mechanisms have been subject to intense investigations. Compelling evidence indicates that rituximab and another CD20 mAb, ofatumumab, must use the body's cellular and humoral immune effector functions to kill malignant cells. Other U.S. Food and Drug Administration-approved mAbs, including obinutuzumab, cetuximab, and trastuzumab, require, in part, these effector mechanisms to eliminate tumor cells. Although gram quantities of mAbs can be administered to patients, our investigations of CD20 mAb-based therapies for chronic lymphocytic leukemia (CLL), including correlative measurements in clinical trials and studies with primary cells and cell lines, indicate that effector mechanisms necessary for mAb activity can be saturated or exhausted if tumor burdens are high, thus substantially compromising the efficacy of high-dose mAb therapy. Under these conditions, another reaction (trogocytosis) predominates in which bound CD20 mAb and CD20 are removed from targeted cells by effector cells that express Fcg receptors, thereby allowing malignant cells to escape unharmed and continue to promote disease pathology. To address this problem, we propose that a low-dose strategy, based on administering 30-50 mg of CD20 mAb three times per week, may be far more effective for CLL than standard dosing because it will minimize effector function saturation and reduce trogocytosis. This approach may have general applicability to other mAbs that use immune effector functions, and could be formulated into a subcutaneous treatment strategy that would be more accessible and possibly more efficacious for patients.

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Section: Possible Generalization To Othermentioning

confidence: 83%

Section: Trogocytosis Of Mab-opsonized Cellsmentioning

confidence: 99%

Analyses of CD20 Monoclonal Antibody–Mediated Tumor Cell Killing Mechanisms: Rational Design of Dosing Strategies

Taylor

Lindorfer

2014

Mol Pharmacol

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“…It is likely that the use of polyclonal Ab raised against highly expressed receptors such as the B cell receptor and their consequent ability to induce extensive hyper crosslinking produce an exaggerated effect when compared to mAb such as rituximab which recognise more discreet antigens and have been demonstrated to produce smaller caps [19] rather than the hemisphere sized caps produced in these early studies. Despite this caveat, several laboratories have shown similar findings with a variety of other mAb (trastuzumab, cetuximab and T101, [50]; epratuzumab, [51]; daclizumab, [52]; CD22/CD20 bispecific, [53] and CD3/Trop-2 bispecific, [54]), demonstrating that shaving does indeed occur on target cells.…”

Section: Antigenic Modulation: Antibody Shavingmentioning

confidence: 82%

Antibody modulation: Limiting the efficacy of therapeutic antibodies

Vaughan

Cragg

Beers

2015

Pharmacological Research

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Monoclonal antibodies (mAb) have revolutionised the way in which we treat disease.From cancer to autoimmunity, antibody therapy has been responsible for some of the most impressive clinical responses observed in the last 2 decades. A key component of this success has been their generally low levels of toxicity, and unique mechanisms of action. These two facets have allowed them to a) be integrated rapidly into clinical practice in combination with conventional radio-and chemotherapies and b) to avoid the resistance mechanisms typically observed with classical small molecule drugs, such as upregulation of drug efflux transporters, dysregulation of apoptosis and mutations in key target enzymes/pathways.Although success with mAb therapies has been impressive, they are also subject to their own resistance mechanisms. In this perspective we discuss the various ways in which mAb therapeutics can be inhibited, concentrating mainly on the ways in which they can be removed from the target cell surface -a process called modulation. This can be achieved either in a cis-fashion on a single cell or in trans, precipitated by engagement with a second phagocytic cell. The evidence for each of these processes will be discussed, in addition to possible therapeutic strategies that might be employed to inhibit or reverse them.Abbreviations: Fc gamma receptor, FcR; monoclonal antibody, mAb

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“…19 These findings have highlighted the importance of developing bioassays that address Fc functions of SM03.…”

Section: Discussionmentioning

confidence: 99%

Surrogate target cells expressing surface anti-idiotype antibody for the clinical evaluation of an internalizing CD22-specific antibody

Leung

Gao

Wang

et al. 2015

mAbs

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Trogocytosis of multiple B-cell surface markers by CD22 targeting with epratuzumab

Cited by 98 publications

References 51 publications

Analyses of CD20 Monoclonal Antibody–Mediated Tumor Cell Killing Mechanisms: Rational Design of Dosing Strategies

Analyses of CD20 Monoclonal Antibody–Mediated Tumor Cell Killing Mechanisms: Rational Design of Dosing Strategies

Antibody modulation: Limiting the efficacy of therapeutic antibodies

Surrogate target cells expressing surface anti-idiotype antibody for the clinical evaluation of an internalizing CD22-specific antibody

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