Evidence map›Paper›PMID 24205120›Full record

ArticlePloS one2013

Physiological level production of antigen-specific human immunoglobulin in cloned transchromosomic cattle.

Akiko Sano, Hiroaki Matsushita, Hua Wu, Jin-An Jiao, Poothappillai Kasinathan, Eddie J Sullivan, Zhongde Wang, Yoshimi Kuroiwa

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.3field-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

19 citing papers in PubMed, 34 citations in OpenAlex.

  1. Review
  2. Article
  3. Special focus issue: passive immunization.Human vaccines & immunotherapeutics · 2022
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Frontiers in immunology · 2019
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Human antibody production in transgenic animals.Archivum immunologiae et therapiae experimentalis · 2015
    Review
  17. Genome engineering in cattle: recent technological advancements.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2015
    Review
  18. Article
  19. Article
4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Akiko SanoKyowa Hakko Kirin, Co., Ltd., Chiyoda-ku, Tokyo, Japan ; Hematech, Inc., Sioux Falls, South Dakota, United States of America.
Hiroaki Matsushita
Hua Wu
Jin-An Jiao
Poothappillai Kasinathan
Eddie J Sullivan
Zhongde Wang
Yoshimi Kuroiwa
University of Sioux Falls · USKyowa Kirin (Japan) · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Therapeutic human polyclonal antibodies (hpAbs) derived from pooled plasma from human donors are Food and Drug Administration approved biologics used in the treatment of a variety of human diseases. Powered by the natural diversity of immune response, hpAbs are effective in treating diseases caused by complex or quickly-evolving antigens such as viruses. We previously showed that transchromosomic (Tc) cattle carrying a human artificial chromosome (HAC) comprising the entire unrearranged human immunoglobulin heavy-chain (hIGH) and kappa-chain (hIGK) germline loci (named as κHAC) are capable of producing functional hpAbs when both of the bovine immunoglobulin mu heavy-chains, bIGHM and bIGHML1, are homozygously inactivated (double knockouts or DKO). However, B lymphocyte development in these Tc cattle is compromised, and the overall production of hpAbs is low. Here, we report the construction of an improved HAC, designated as cKSL-HACΔ, by incorporating all of the human immunoglobulin germline loci into the HAC. Furthermore, for avoiding the possible human-bovine interspecies incompatibility between the human immunoglobulin mu chain protein (hIgM) and bovine transmembrane α and β immunoglobulins (bIgα and bIgβ) in the pre-B cell receptor (pre-BCR) complex, we partially replaced (bovinized) the hIgM constant domain with the counterpart of bovine IgM (bIgM) that is involved in the interaction between bIgM and bIgα/Igβ; human IgM bovinization would also improve the functionality of hIgM in supporting B cell activation and proliferation. We also report the successful production of DKO Tc cattle carrying the cKSL-HACΔ (cKSL-HACΔ/DKO), the dramatic improvement of B cell development in these cattle and the high level production of hpAbs (as measured for the human IgG isotype) in the plasma. We further demonstrate that, upon immunization by tumor immunogens, high titer tumor immunogen-specific human IgG (hIgG) can be produced from such Tc cattle.

Indexed as

AnimalsB-LymphocytesCattleCell ProliferationChromosomes, Artificial, HumanHumansImmunoglobulin GImmunoglobulin Heavy ChainsImmunoglobulin MImmunoglobulin mu-ChainsImmunoglobulinsImmunoglobulin GImmunoglobulin Heavy ChainsImmunoglobulin MImmunoglobulin mu-ChainsImmunoglobulins

Identifiers

PMID24205120
PMCPMC3813428
OpenAlexW1982191165

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.