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Cancer Vaccines Co-Targeting HER2/Neu and IGF1R

Laboratory of Immunology and Biology of Metastasis, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Viale Filopanti 22, I-40126 Bologna, Italy
Laboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, I-40136 Bologna, Italy
Department of Bioscience and Biotechnology, University of Camerino, I-62032 Camerino, Italy
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;
Received: 27 March 2019 / Accepted: 9 April 2019 / Published: 11 April 2019
(This article belongs to the Special Issue Cancer Vaccines: Research and Applications)
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(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

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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.

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