Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Enhanced antitumor efficacy of an oncolytic adenovirus armed with an EGFR-targeted BiTE using menstrual blood-derived mesenchymal stem cells as carriers

Cancer Gene Therapy volume 27, pages 383–388 (2020)Cite this article

Subjects

Abstract

Poor tumor targeting of oncolytic adenoviruses (OAdv) after systemic administration is considered a major limitation for virotherapy of disseminated cancers. The benefit of using mesenchymal stem cells as cell carriers for OAdv tumor targeting is currently evaluated not only in preclinical models but also in clinical trials. In this context, we have previously demonstrated the enhanced antitumor efficacy of OAdv-loaded menstrual blood-derived mesenchymal stem cells (MenSCs). However, although significant, the antitumor efficacy obtained was modest, and we hypothesized that a greater antitumor efficacy could be obtained arming the OAdv with a therapeutic transgene. Here we show that combining MenSCs with ICOVIR15-cBiTE, an OAdv expressing an epidermal growth factor receptor (EGFR)-targeting bispecific T-cell engager (cBiTE), enhances the antitumor efficacy compared to MenSCs loaded with the unarmed virus ICOVIR15. We found that MenSCs properly produce cBiTE after viral infection leading to a greater antitumor potency both in vitro and in vivo. These findings indicate the mutual benefit of combining MenSCs and armed OAdv and support the combination of ICOVIR15-cBiTE and MenSCs as a cancer treatment.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1

Similar content being viewed by others

References

  1. Rosewell Shaw A, Suzuki M. Recent advances in oncolytic adenovirus therapies for cancer. Curr Opin Virol. 2016;21:9–15.

    Article  Google Scholar 

  2. Khare R, Chen CY, Weaver EA, Barry MA. Advances and future challenges in adenoviral vector pharmacology and targeting. Curr Gene Ther. 2011;11:241–58.

    Article  CAS  Google Scholar 

  3. Rodriguez-Garcia A, Svensson E, Gil-Hoyos R, Fajardo CA, Rojas LA, Arias-Badia M, et al. Insertion of exogenous epitopes in the E3-19K of oncolytic adenoviruses to enhance TAP-independent presentation and immunogenicity. Gene Ther. 2015;22:596–601.

    Article  CAS  Google Scholar 

  4. Uchibori R, Tsukahara T, Ohmine K, Ozawa K. Cancer gene therapy using mesenchymal stem cells. Int J Hematol. 2014;99:377–82.

    Article  CAS  Google Scholar 

  5. Moreno R, Fajardo CA, Farrera-Sal M, Perise-Barrios AJ, Morales-Molina A, Al-Zaher AA, et al. Enhanced antitumor efficacy of oncolytic adenovirus-loaded menstrual blood-derived mesenchymal stem cells in combination with peripheral blood mononuclear cells. Mol Cancer Ther. 2019;18:127–38.

    Article  CAS  Google Scholar 

  6. Fajardo CA, Guedan S, Rojas LA, Moreno R, Arias-Badia M, de Sostoa J, et al. Oncolytic adenoviral delivery of an EGFR-targeting T-cell engager improves antitumor efficacy. Cancer Res. 2017;77:2052–63.

    Article  CAS  Google Scholar 

  7. Baeuerle PA, Kufer P, Bargou R. BiTE: teaching antibodies to engage T-cells for cancer therapy. Curr Opin Mol Ther. 2009;11:22–30.

    CAS  PubMed  Google Scholar 

  8. Offner S, Hofmeister R, Romaniuk A, Kufer P, Baeuerle PA. Induction of regular cytolytic T cell synapses by bispecific single-chain antibody constructs on MHC class I-negative tumor cells. Mol Immunol. 2006;43:763–71.

    Article  CAS  Google Scholar 

  9. Moreno R, Rojas LA, Villellas FV, Soriano VC, Garcia-Castro J, Fajardo CA, et al. Human menstrual blood-derived mesenchymal stem cells as potential cell carriers for oncolytic adenovirus. Stem cells Int. 2017;2017:3615729.

    Article  CAS  Google Scholar 

  10. Melen GJ, Franco-Luzon L, Ruano D, Gonzalez-Murillo A, Alfranca A, Casco F, et al. Influence of carrier cells on the clinical outcome of children with neuroblastoma treated with high dose of oncolytic adenovirus delivered in mesenchymal stem cells. Cancer Lett. 2016;371:161–70.

    Article  CAS  Google Scholar 

  11. Alfano AL, Nicola Candia A, Cuneo N, Guttlein LN, Soderini A, Rotondaro C, et al. Oncolytic adenovirus-loaded menstrual blood stem cells overcome the blockade of viral activity exerted by ovarian cancer ascites. Mol Ther Oncolytics. 2017;6:31–44.

    Article  CAS  Google Scholar 

  12. Szoor A, Vaidya A, Velasquez MP, Mei Z, Galvan DL, Torres D, et al. T cell-activating mesenchymal stem cells as a biotherapeutic for HCC. Mol Ther Oncolytics. 2017;6:69–79.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank CERCA Program/Generalitat de Catalunya for their institutional support. The authors also thank Dolores Ramos and Silvia Torres for their lab technical support and Vanessa Cervera for samples processing. This work was supported by the Asociación Española Contra el Cáncer, BIO2017-897554-C2-1-R grant to R. Alemany from the Ministerio de Economía y Competitividad of Spain, Adenonet BIO2015-68990-REDT to R. Alemany from the Ministerio de Economía y Competitividad of Spain, Red ADVANCE(CAT) project COMRDI15-1-0013 to R. Alemany from Ris3CAT and 2017SGR449 research grant to RA from the ‘Generalitat de Catalunya’. Cofunded by the European Regional Development Fund, a way to Build Europe to RA.

Author information

Authors and Affiliations

  1. Virotherapy and Gene therapy Group, Oncobell and ProCure Programs, IDIBELL-Instituto Catalan d’Oncología, l’Hospitalet de Llobregat, Barcelona, Spain

    Paula Barlabé, Jana de Sostoa, Carlos Alberto Fajardo, Ramon Alemany & Rafael Moreno

Authors
  1. Paula Barlabé
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jana de Sostoa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carlos Alberto Fajardo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ramon Alemany
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rafael Moreno
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rafael Moreno.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Barlabé, P., Sostoa, J.d., Fajardo, C.A. et al. Enhanced antitumor efficacy of an oncolytic adenovirus armed with an EGFR-targeted BiTE using menstrual blood-derived mesenchymal stem cells as carriers. Cancer Gene Ther 27, 383–388 (2020). https://doi.org/10.1038/s41417-019-0110-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41417-019-0110-1

This article is cited by

Search

Advanced search

Quick links