Evidence map›Paper›PMID 31506285›Full record

ArticleBlood advances2019

Mitigation of T-cell dependent immunogenicity by reengineering factor VIIa analogue.

Wojciech Jankowski, Joseph McGill, H A Daniel Lagassé, Stepan Surov, Gary Bembridge, Campbell Bunce, Edward Cloake, Mark H Fogg, Katarzyna I Jankowska, Abdul Khan and 3 more

Open access · goldAbstract read
In one paragraph

Article in Blood advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.7field-weighted citation impact, top 28% 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

9 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Reducing Immunogenicity by Design: Approaches to Minimize Immunogenicity of Monoclonal Antibodies.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024
    Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
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

13 authors at 3 institutions in 3 countries.

Wojciech JankowskiHemostasis Branch, Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD.ORCID 0000-0002-7000-9057
Joseph McGillHemostasis Branch, Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD.ORCID 0000-0002-3369-3822
H A Daniel LagasséHemostasis Branch, Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD.
Stepan SurovHemostasis Branch, Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD.
Gary BembridgeAbzena, Babraham Research Campus, Cambridge, United Kingdom.
Campbell BunceAbzena, Babraham Research Campus, Cambridge, United Kingdom.
Edward CloakeAbzena, Babraham Research Campus, Cambridge, United Kingdom.
Mark H FoggAbzena, Babraham Research Campus, Cambridge, United Kingdom.
Katarzyna I JankowskaLaboratory of Cellular Hematology, Division of Blood Components and Devices, Office of Blood Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD; and.
Abdul KhanDepartment of Chemistry and Chemical Biology, Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, NJ.
Joseph MarcotrigianoDepartment of Chemistry and Chemical Biology, Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, NJ.
Mikhail V OvanesovHemostasis Branch, Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD.
Zuben E SaunaHemostasis Branch, Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD.ORCID 0000-0001-8202-5188
Center for Biologics Evaluation and Research · USAbzena (United Kingdom) · GBRutgers, The State University of New Jersey · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Vatreptacog alfa (VA), a recombinant activated human factor VII (rFVIIa) variant with 3 amino acid substitutions, was developed to provide increased procoagulant activity in hemophilia patients with inhibitors to factor VIII or factor IX. In phase 3 clinical trials, changes introduced during the bioengineering of VA resulted in the development of undesired anti-drug antibodies in some patients, leading to the termination of a potentially promising therapeutic protein product. Here, we use preclinical biomarkers associated with clinical immunogenicity to validate our deimmunization strategy applied to this bioengineered rFVIIa analog. The reengineered rFVIIa analog variants retained increased intrinsic thrombin generation activity but did not elicit T-cell responses in peripheral blood mononuclear cells isolated from 50 HLA typed subjects representing the human population. Our algorithm, rational immunogenicity determination, offers a broadly applicable deimmunizing strategy for bioengineered proteins.

Indexed as

Blood Coagulation TestsCells, CulturedFactor VIIaHemophilia AHumansImmunogenetic PhenomenaProtein EngineeringRecombinant ProteinsThrombinT-LymphocytesFactor VIIarecombinant FVIIaRecombinant ProteinsThrombinvatreptacog alfa

Identifiers

PMID31506285
PMCPMC6737420
OpenAlexW2972847538

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.