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Tome-Amat, JaimeAuthor

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November 18, 2019
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Inclusion of a Furin Cleavage Site Enhances Antitumor Efficacy against Colorectal Cancer Cells of Ribotoxin alpha-Sarcin- or RNase T1-Based Immunotoxins

Publicated to: Toxins. 11 (10): E593- - 2019-10-12 11(10), DOI: 10.3390/toxins11100593

Authors:

Ruiz-de-la-Herran, Javier; Tome-Amat, Jaime; Lazaro-Gorines, Rodrigo; Gavilanes, Jose G.; Lacadena, Javier;
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Affiliations

Univ Complutense Madrid, Fac Ciencias Quim, Dept Bioquim & Biol Mol, E-28040 Madrid, Spain - Author
UPM, Ctr Plant Biotechnol & Genom, INIA, Madrid 28223, Spain - Author

Abstract

Immunotoxins are chimeric molecules that combine the specificity of an antibody to recognize and bind tumor antigens with the potency of the enzymatic activity of a toxin, thus, promoting the death of target cells. Among them, RNases-based immunotoxins have arisen as promising antitumor therapeutic agents. In this work, we describe the production and purification of two new immunoconjugates, based on RNase T1 and the fungal ribotoxin alpha-sarcin, with optimized properties for tumor treatment due to the inclusion of a furin cleavage site. Circular dichroism spectroscopy, ribonucleolytic activity studies, flow cytometry, fluorescence microscopy, and cell viability assays were carried out for structural and in vitro functional characterization. Our results confirm the enhanced antitumor efficiency showed by these furin-immunotoxin variants as a result of an improved release of their toxic domain to the cytosol, favoring the accessibility of both ribonucleases to their substrates. Overall, these results represent a step forward in the design of immunotoxins with optimized properties for potential therapeutic application in vivo.
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Keywords

colorectal cancerfurinimmunotoxinintracellular traffickingribotoxinrnase t1?-sarcinA33 antigenAlpha-sarcinCell line, tumorClinical-trialsColonic neoplasmsColorectal cancerEndoribonucleasesFungal proteinsFurinGolgiHumansImmunoconjugatesImmunotoxinImmunotoxinsIntracellular traffickingMechanismProprotein-processing enzymeRecombinant immunotoxinsRestrictocinRibonuclease t1Ribonuclease-t1RibotoxinRnase t1ToxinΑ-sarcin

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Toxins due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2019, it was in position 21/92, thus managing to position itself as a Q1 (Primer Cuartil), in the category Toxicology.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2025-12-22:

  • WoS: 6
  • Scopus: 10
  • Europe PMC: 5
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Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-12-22:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 17.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 17 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 21.
  • The number of mentions on the social network X (formerly Twitter): 7 (Altmetric).
  • The number of mentions in news outlets: 2 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: https://oa.upm.es/63636/

As a result of the publication of the work in the institutional repository, statistical usage data has been obtained that reflects its impact. In terms of dissemination, we can state that, as of

  • Views: 499
  • Downloads: 367
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Awards linked to the item

This research was funded by the Universidad Complutense de Madrid, grant numbers PR41/17-21004 and PR75/18-21563.
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