Evidence map›Paper›PMID 29595951›Full record

ArticleACS nano2018

Amplification of CD20 Cross-Linking in Rituximab-Resistant B-Lymphoma Cells Enhances Apoptosis Induction by Drug-Free Macromolecular Therapeutics.

Lian Li, Jiyuan Yang, Jiawei Wang, Jindřich Kopeček

Abstract read
In one paragraph

Article in ACS nano, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.0field-weighted citation impact, top 6% 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, 59 citations in OpenAlex.

  1. Review
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  8. Multi-targeted immunotherapeutics to treat B cell malignancies.Journal of controlled release : official journal of the Controlled Release Society · 2023
    Review
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  19. Polymer nanomedicines.Advanced drug delivery reviews · 2020
    Review
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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

4 authors at 1 institution in 1 country.

Lian Li
Jiyuan Yang
Jiawei Wang
Jindřich KopečekORCID 0000-0002-4451-6944
University of Utah · US

Funding

UTAH REGIONAL CANCER CENTERP30CA042014 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI KATHARINE S ULLMAN · 1986 to 2026
$72.6M
Drug-Free Macromolecular TherapeuticsR01GM095606 · NIGMS · UNIVERSITY OF UTAH · PI KOPECEK, JINDRICH H. · 2011 to 2018
$2.3M
NIGMS NIH HHS R01 GM095606
6 · The paper itself

Abstract

Although the CD20-targeted monoclonal antibody rituximab (RTX) has revolutionized the therapeutic landscape for B-cell malignancy, relapsed and refractory disease due to RTX resistance continue to constitute major challenges, illustrating the need for better therapies. Here, we apply drug-free macromolecular therapeutics (DFMT) that amplifies CD20 cross-linking to enhance apoptosis in RTX-resistant cells. Bispecific engager (anti-CD20 Fab' conjugated with oligonucleotide1) pretargets CD20 and the deletion of Fc-region minimizes its premature endocytosis in resistant cells that rapidly internalize and consume CD20/RTX complexes. Second-step delivery of multivalent polymeric effector (linear copolymer conjugated with multiple copies of complementary oligonucleotide 2) simultaneously hybridizes multiple CD20-bound engagers and strengthens CD20 ligation. Moreover, the restoration of CD20 expression by the pretreatment of cells with a polymer-gemcitabine conjugate, a CD20 expression enhancer, unleashes the full potential of DFMT in the CD20-deficient resistant cells. Hence, amplification of CD20 cross-linking is achieved by (1) the enhancement of surface CD20 accessibility, (2) the increase in CD20 expression, and (3) multimeric CD20 binding, which ultimately translates into the amplified activation of a wide range of innate apoptotic responses. We demonstrated that the altered molecular signaling pathway that originally results in RTX resistance could be circumvented and compensated by other DFMT-augmented pathways. Of note, our preliminary data provide proof-of-concept that CD20 cross-linking amplification emerges as an important strategy for overcoming RTX resistance.

Indexed as

AnimalsAntigens, CD20Antineoplastic AgentsApoptosisCell Line, TumorCross-Linking ReagentsHumansLymphoma, B-CellMiceMice, Inbred NODMice, SCIDRituximabAntigens, CD20Antineoplastic AgentsCross-Linking ReagentsRituximabdrug-free macromolecular therapeuticsHPMA copolymernon-Hodgkin lymphomareceptor cross-linkingrituximab resistance

Identifiers

PMID29595951
PMCPMC5916500
OpenAlexW2795100859

What OpenQuestion holds

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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.