Evidence map›Paper›PMID 25949896›Full record

ArticleOncoimmunology2015

Neutralization of membrane complement regulators improves complement-dependent effector functions of therapeutic anticancer antibodies targeting leukemic cells.

Srinivas Mamidi, Simon Höne, Claudia Teufel, Leopold Sellner, Thorsten Zenz, Michael Kirschfink

Open access · goldAbstract read
In one paragraph

Article in Oncoimmunology, 2015. 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
2.2field-weighted citation impact, top 12% 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, 42 citations in OpenAlex.

  1. Article
  2. Complement system in tumor growth and metastases.British journal of cancer · 2026
    Review
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  17. Role of C5b-9 and RGC-32 in Cancer.Frontiers in immunology · 2019
    Review
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  19. Article
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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

6 authors at 4 institutions in 3 countries.

Srinivas MamidiInstitute for Immunology; University of Heidelberg ; Heidelberg, Germany.
Simon HöneInstitute for Immunology; University of Heidelberg ; Heidelberg, Germany.
Claudia TeufelInstitute for Immunology; University of Heidelberg ; Heidelberg, Germany.
Leopold SellnerDepartment of Translational Oncology; National Center for Tumour Diseases (NCT) and German Cancer Research Center (DKFZ) ; Heidelberg, Germany ; Department of Medicine V; University of Heidelberg ; Heidelberg, Germany.
Thorsten ZenzDepartment of Translational Oncology; National Center for Tumour Diseases (NCT) and German Cancer Research Center (DKFZ) ; Heidelberg, Germany ; Department of Medicine V; University of Heidelberg ; Heidelberg, Germany.
Michael KirschfinkInstitute for Immunology; University of Heidelberg ; Heidelberg, Germany.
Institute of Immunology · HRHeidelberg University · USHeidelberg University · DENational Center for Tumor Diseases · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Complement-dependent cytotoxicity (CDC) is one of the effector mechanisms mediated by therapeutic anticancer monoclonal antibodies (mAbs). However, the efficacy of antibodies is limited by the resistance of malignant cells to complement attack, primarily due to the over-expression of one or more membrane complement regulatory proteins (mCRPs) CD46, CD55, and CD59. CD20-positive Burkitt lymphoma Raji cells and primary CLL cells are resistant to rituximab (RTX)-induced CDC whereas ofatumumab (OFA) proved to be more efficient in cell killing. Primary CLL cells but not CD52-positive acute lymphoblastic leukemia (ALL) REH cells were sensitive to alemtuzumab (ALM)-induced CDC. Upon combined inhibition on Raji and CLL cells by mCRPs-specific siRNAs or neutralizing antibodies, CDC induced by RTX and by OFA was augmented. Similarly, CDC of REH cells was enhanced after mCRPs were inhibited upon treatment with ALM. All mAbs induced C3 opsonization, which was significantly augmented upon blocking mCRPs. C3 opsonization led to enhanced cell-mediated cytotoxicity of leukemia cells exposed to PBLs or macrophages. Furthermore, opsonized CLL cells were efficiently phagocytized by macrophages. Our results provide conclusive evidence that inhibition of mCRPs expression sensitizes leukemic cells to complement attack thereby enhancing the therapeutic effect of mAbs targeting leukemic cells.

Indexed as

ADCC, antibody-dependent cellular cytotoxicityalemtuzumabALM, AlemtuzumabCDCC, complement-dependent cellular cytotoxicityCDC, complement-dependent cytotoxicitychronic lymphocytic leukemiacomplement-dependent cytotoxicitycomplement regulatory proteinsMAC, membrane attack complexmCRP, membrane-bound complement regulatory proteinNHS, Normal Human SerumOFA, OfatumumabofatumumabopsonizationPBLs, peripheral blood leukocytesrituximabRTX, RituximabsiRNA, small interfering RNATRX, Trastuzumab

Identifiers

PMID25949896
PMCPMC4404820
OpenAlexW2072011311

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.