Next Article in Journal
Establishment and Characterization of a New Intrahepatic Cholangiocarcinoma Cell Line Resistant to Gemcitabine
Previous Article in Journal
Statins Do Not Directly Inhibit the Activity of Major Epigenetic Modifying Enzymes
Previous Article in Special Issue
Exploratory Study of the Effect of IMA950/Poly-ICLC Vaccination on Response to Bevacizumab in Relapsing High-Grade Glioma Patients
Article Menu
Issue 4 (April) cover image

Export Article

Open AccessArticle

Cancer Vaccines Co-Targeting HER2/Neu and IGF1R

1
Laboratory of Immunology and Biology of Metastasis, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Viale Filopanti 22, I-40126 Bologna, Italy
2
Laboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, I-40136 Bologna, Italy
3
Department of Bioscience and Biotechnology, University of Camerino, I-62032 Camerino, Italy
4
Unit of Clinical Immunology, Allergy and Advanced Biotechnologies, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, I-42122 Reggio Emilia
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2019, 11(4), 517; https://doi.org/10.3390/cancers11040517
Received: 27 March 2019 / Accepted: 9 April 2019 / Published: 11 April 2019
(This article belongs to the Special Issue Cancer Vaccines: Research and Applications)
  |  
PDF [1592 KB, uploaded 19 April 2019]
  |  

Abstract

(1) Background: Human epidermal growth factor receptor 2 (HER2)/neu-driven carcinogenesis is delayed by preventive vaccines able to elicit autochthonous antibodies against HER2/neu. Since cooperation between different receptor tyrosine kinases (RTKs) can occur in human as well as in experimental tumors, we investigated the set-up of DNA and cell vaccines to elicit an antibody response co-targeting two RTKs: HER2/neu and the Insulin-like Growth Factor Receptor-1 (IGF1R). (2) Methods: Plasmid vectors carrying the murine optimized IGF1R sequence or the human IGF1R isoform were used as electroporated DNA vaccines. IGF1R plasmids were transfected in allogeneic HER2/neu-positive IL12-producing murine cancer cells to obtain adjuvanted cell vaccines co-expressing HER2/neu and IGF1R. Vaccination was administered in the preneoplastic stage to mice prone to develop HER2/neu-driven, IGF1R-dependent rhabdomyosarcoma. (3) Results: Electroporated DNA vaccines for murine IGF1R did not elicit anti-mIGF1R antibodies, even when combined with Treg-depletion and/or IL12, while DNA vaccines carrying the human IGF1R elicited antibodies recognizing only the human IGF1R isoform. Cell vaccines co-expressing HER2/neu and murine or human IGF1R succeeded in eliciting antibodies recognizing the murine IGF1R isoform. Cell vaccines co-targeting HER2/neu and murine IGF1R induced the highest level of anti-IGF1R antibodies and nearly significantly delayed the onset of spontaneous rhabdomyosarcomas. (4) Conclusions: Multi-engineered adjuvanted cancer cell vaccines can break the tolerance towards a highly tolerized RTK, such as IGF1R. Cell vaccines co-targeting HER2/neu and IGF1R elicited low levels of specific antibodies that slightly delayed onset of HER2/neu-driven, IGF1R-dependent tumors. View Full-Text
Keywords: cancer vaccines; HER2/neu; IGF1R; muscle neoplasms; DNA vaccines cancer vaccines; HER2/neu; IGF1R; muscle neoplasms; DNA vaccines
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

De Giovanni, C.; Landuzzi, L.; Palladini, A.; Ianzano, M.L.; Nicoletti, G.; Ruzzi, F.; Amici, A.; Croci, S.; Nanni, P.; Lollini, P.-L. Cancer Vaccines Co-Targeting HER2/Neu and IGF1R. Cancers 2019, 11, 517.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top