Evidence map›Paper›PMID 33212776›Full record

ArticleAntibodies (Basel, Switzerland)2020

Enhancing CDC and ADCC of CD19 Antibodies by Combining Fc Protein-Engineering with Fc Glyco-Engineering.

Sophia Roßkopf, Klara Marie Eichholz, Dorothee Winterberg, Katarina Julia Diemer, Sebastian Lutz, Ira Alexandra Münnich, Katja Klausz, Thies Rösner, Thomas Valerius, Denis Martin Schewe and 4 more

Open access · goldAbstract read
In one paragraph

Article in Antibodies (Basel, Switzerland), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.8field-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

14 citing papers in PubMed, 24 citations in OpenAlex.

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  3. Effectors of the Future: Universal Chimeric Antigen Receptor.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2025
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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

14 authors at 2 institutions in 1 country.

Sophia RoßkopfDivision of Stem Cell Transplantation and Immunotherapy, Department of Medicine II Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
Klara Marie EichholzDivision of Stem Cell Transplantation and Immunotherapy, Department of Medicine II Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
Dorothee WinterbergPediatric Hematology/Oncology, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
Katarina Julia DiemerDivision of Stem Cell Transplantation and Immunotherapy, Department of Medicine II Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
Sebastian LutzDepartment of Transfusion Medicine, Cell Therapeutics and Hemostaseology, University Hospital, LMU Munich, 81377 Munich, Germany.
Ira Alexandra MünnichDepartment of Transfusion Medicine, Cell Therapeutics and Hemostaseology, University Hospital, LMU Munich, 81377 Munich, Germany.
Katja KlauszDivision of Stem Cell Transplantation and Immunotherapy, Department of Medicine II Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
Thies RösnerDivision of Stem Cell Transplantation and Immunotherapy, Department of Medicine II Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
Thomas ValeriusDivision of Stem Cell Transplantation and Immunotherapy, Department of Medicine II Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
Denis Martin SchewePediatric Hematology/Oncology, Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.ORCID 0000-0002-1070-0217
Andreas HumpeDepartment of Transfusion Medicine, Cell Therapeutics and Hemostaseology, University Hospital, LMU Munich, 81377 Munich, Germany.
Martin GramatzkiDivision of Stem Cell Transplantation and Immunotherapy, Department of Medicine II Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
Matthias PeippDivision of Stem Cell Transplantation and Immunotherapy, Department of Medicine II Christian-Albrechts-University Kiel and University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany.
Christian KellnerDepartment of Transfusion Medicine, Cell Therapeutics and Hemostaseology, University Hospital, LMU Munich, 81377 Munich, Germany.
Christian-Albrechts-Universität zu Kiel · DELudwig-Maximilians-Universität München · DE

Funding

Deutsche Krebshilfe 70110951Deutsche Krebshilfe C.K. + D.M.S.José Carreras Leukämie-Stiftung C.K. + D.M.S.Wilhelm Sander-Stiftung M.P. + C.K.
6 · The paper itself

Abstract

backgroundNative cluster of differentiation (CD) 19 targeting antibodies are poorly effective in triggering antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), which are crucial effector functions of therapeutic antibodies in cancer immunotherapy. Both functions can be enhanced by engineering the antibody's Fc region by altering the amino acid sequence (Fc protein-engineering) or the Fc-linked glycan (Fc glyco-engineering). We hypothesized that combining Fc glyco-engineering with Fc protein-engineering will rescue ADCC and CDC in CD19 antibodies.

resultsFour versions of a CD19 antibody based on tafasitamab's V-regions were generated: a native IgG1, an Fc protein-engineered version with amino acid exchanges S267E/H268F/S324T/G236A/I332E (EFTAE modification) to enhance CDC, and afucosylated, Fc glyco-engineered versions of both to promote ADCC. Irrespective of fucosylation, antibodies carrying the EFTAE modification had enhanced C1q binding and were superior in inducing CDC. In contrast, afucosylated versions exerted an enhanced affinity to Fcγ receptor IIIA and had increased ADCC activity. Of note, the double-engineered antibody harboring the EFTAE modification and lacking fucose triggered both CDC and ADCC more efficiently.

conclusionsFc glyco-engineering and protein-engineering could be combined to enhance ADCC and CDC in CD19 antibodies and may allow the generation of antibodies with higher therapeutic efficacy by promoting two key functions simultaneously.

Indexed as

antibody-dependent cell-mediated cytotoxicity (ADCC)antibody therapyCD19cluster of differentiation 19 (CD19)complement-dependent cytotoxicity (CDC)Fc engineeringFc fragment crystallizable (Fc)

Identifiers

PMID33212776
PMCPMC7709100
OpenAlexW3101203667

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.