Evidence map›Paper›PMID 24944188›Full record

ReviewMolecular pharmacology2014

Analyses of CD20 monoclonal antibody-mediated tumor cell killing mechanisms: rational design of dosing strategies.

Ronald P Taylor, Margaret A Lindorfer

Open access · bronzeAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Molecular pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
4.3field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Monocytes and Granulocytes Reduce CD38 Expression Levels on Myeloma Cells in Patients Treated with Daratumumab.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017
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  18. Regulation of expression of MLAA-34 gene through transcriptional factors E2F1 and MZF-1.International journal of clinical and experimental pathology · 2019
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Ronald P TaylorDepartment of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia rpt@virginia.edu.
Margaret A LindorferDepartment of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia.
University of Virginia · US

Funding

Women's Oncology Program - WONP30CA044579 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Jay William FOX · 1987 to 2026
$72.1M
NCI NIH HHS P30 CA044579NCI NIH HHS P30-CA044579
6 · The paper itself

Abstract

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 Fcγ 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.

Indexed as

AnimalsAntibodies, MonoclonalAntigens, CD20Antineoplastic AgentsClinical Trials, Phase III as TopicHumansNeoplasmsAntibodies, MonoclonalAntigens, CD20Antineoplastic Agents

Identifiers

PMID24944188
PMCPMC4201137
OpenAlexW2109775395

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.