Evidence map›Paper›PMID 31121497›Full record

ArticleCytokine2019

Amino acid residues involved in the heparin-binding activity of murine IL-12 in the context of an antibody-cytokine fusion protein.

Rosendo Luria-Pérez, Pierre V Candelaria, Tracy R Daniels-Wells, José A Rodríguez, Gustavo Helguera, Manuel L Penichet

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cytokine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.2field-weighted citation impact, top 46% 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

3 citing papers in PubMed, 7 citations in OpenAlex.

  1. Heparan Sulfate Proteoglycans in Immunity.Proteoglycan research · 2026
    Article
  2. Article
  3. Review
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 2 institutions in 1 country.

Rosendo Luria-PérezDivision of Surgical Oncology, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Pierre V CandelariaDivision of Surgical Oncology, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Tracy R Daniels-WellsDivision of Surgical Oncology, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
José A RodríguezDepartment of Chemistry and Biochemistry at UCLA, Los Angeles, CA, USA; UCLA-DOE Institute, Los Angeles, CA, USA; The Molecular Biology Institute, UCLA, CA, USA.
Gustavo HelgueraDivision of Surgical Oncology, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA. Electronic address: gustavoh@ibyme.conicet.gov.ar.
Manuel L PenichetDivision of Surgical Oncology, Department of Surgery, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; The Molecular Biology Institute, UCLA, CA, USA; Jonsson Comprehensive Cancer Center, UCLA, CA, USA; UCLA AIDS Institute, Los Angeles, CA, USA. Electronic address: penichet@mednet.ucla.edu.
University of California, Los Angeles · USUniversity of Colorado Denver · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
Virology CoreP30AI028697 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ANTON, PETER A · 1991 to 2018
$39.9M
Novel Nanopolymers to Inhibit Angiogenesis and Increase the Anti-tumor ImmunityR01CA136841 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LJUBIMOVA, JULIA Y, PENICHET, MANUEL L · 2010 to 2014
$2.7M
A Novel Anti-HER2/neu IgE for Breast Cancer TherapyR01CA181115 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PENICHET, MANUEL L · 2014 to 2018
$2.5M
Howard Hughes Medical InstituteNCI NIH HHS P30 CA016042NCI NIH HHS R01 CA136841NCI NIH HHS R01 CA181115NIAID NIH HHS P30 AI028697
6 · The paper itself

Abstract

An antibody-cytokine fusion protein, composed of the murine single-chain cytokine interleukin-12 (IL-12) genetically fused to a human IgG3 specific for the human tumor-associated antigen HER2/neu maintains antigen binding, cytokine bioactivity, and IL-12 heparin-binding activity. This latter property is responsible for the binding of the cytokine to glycosaminoglycans (GAGs) on the cell surface and the extracellular matrix and has been implicated in modulating IL-12 bioactivity. Previous studies indicate that the p40 subunit of human and murine IL-12 is responsible for the heparin-binding activity of this heterodimeric cytokine. In the present study we used bioinformatic analysis and site-directed mutagenesis to develop a version of the antibody-(IL-12) fusion protein without heparin-binding activity. This was accomplished by replacing the basic arginine (R) and lysine (K) residues in the cluster of amino acids 254-260 (RKKEKMK) of the murine IL-12 p40 subunit by the neutral non-polar amino acid alanine (A), generating an AAAEAMA mutant fusion protein. ELISA and flow cytometry demonstrated that the antibody fusion protein lacks heparin-binding activity but retains antigen binding. A T-cell proliferation assay showed IL-12 bioactivity in this construct. However, the IL-12 bioactivity is decreased compared to its non-mutated counterpart, which is consistent with an ancillary role of the heparin-binding site of IL-12 in modulating its activity. Thus, we have defined a cluster of amino acid residues with a crucial role in the heparin-binding activity of murine IL-12 in the context of an antibody-cytokine fusion protein.

Indexed as

Amino AcidsAnimalsAntibodiesAntigens, NeoplasmBinding SitesCell Line, TumorCell ProliferationErb-b2 Receptor Tyrosine KinasesHeparinHumansInterleukin-12MiceProtein BindingRecombinant Fusion ProteinsT-LymphocytesAmino AcidsAntibodiesAntigens, NeoplasmErb-b2 Receptor Tyrosine KinasesHeparinInterleukin-12Recombinant Fusion ProteinsAntibody fusion proteinCytokineGlycosaminoglycansHeparinHER2/neuInterleukin-12

Identifiers

PMID31121497
PMCPMC7007190
OpenAlexW2946365548

What OpenQuestion holds

Textmetadata
LicenceTDM
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.