Cancer Vaccines Co-Targeting HER2/Neu and IGF1R
(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 tum...
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-04-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/4/517 |
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| author | Carla De Giovanni Lorena Landuzzi Arianna Palladini Marianna Lucia Ianzano Giordano Nicoletti Francesca Ruzzi Augusto Amici Stefania Croci Patrizia Nanni Pier-Luigi Lollini |
| author_facet | Carla De Giovanni Lorena Landuzzi Arianna Palladini Marianna Lucia Ianzano Giordano Nicoletti Francesca Ruzzi Augusto Amici Stefania Croci Patrizia Nanni Pier-Luigi Lollini |
| author_sort | Carla De Giovanni |
| collection | DOAJ |
| description | (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. |
| first_indexed | 2024-03-12T08:06:27Z |
| format | Article |
| id | doaj.art-ff164551ca18433a8299249b163d7cd7 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T08:06:27Z |
| publishDate | 2019-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-ff164551ca18433a8299249b163d7cd72023-09-02T19:29:20ZengMDPI AGCancers2072-66942019-04-0111451710.3390/cancers11040517cancers11040517Cancer Vaccines Co-Targeting HER2/Neu and IGF1RCarla De Giovanni0Lorena Landuzzi1Arianna Palladini2Marianna Lucia Ianzano3Giordano Nicoletti4Francesca Ruzzi5Augusto Amici6Stefania Croci7Patrizia Nanni8Pier-Luigi Lollini9Laboratory of Immunology and Biology of Metastasis, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Viale Filopanti 22, I-40126 Bologna, ItalyLaboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, I-40136 Bologna, ItalyLaboratory of Immunology and Biology of Metastasis, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Viale Filopanti 22, I-40126 Bologna, ItalyLaboratory of Immunology and Biology of Metastasis, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Viale Filopanti 22, I-40126 Bologna, ItalyLaboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, I-40136 Bologna, ItalyLaboratory of Immunology and Biology of Metastasis, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Viale Filopanti 22, I-40126 Bologna, ItalyDepartment of Bioscience and Biotechnology, University of Camerino, I-62032 Camerino, ItalyUnit of Clinical Immunology, Allergy and Advanced Biotechnologies, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, I-42122 Reggio EmiliaLaboratory of Immunology and Biology of Metastasis, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Viale Filopanti 22, I-40126 Bologna, ItalyLaboratory of Immunology and Biology of Metastasis, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Viale Filopanti 22, I-40126 Bologna, Italy(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.https://www.mdpi.com/2072-6694/11/4/517cancer vaccinesHER2/neuIGF1Rmuscle neoplasmsDNA vaccines |
| spellingShingle | Carla De Giovanni Lorena Landuzzi Arianna Palladini Marianna Lucia Ianzano Giordano Nicoletti Francesca Ruzzi Augusto Amici Stefania Croci Patrizia Nanni Pier-Luigi Lollini Cancer Vaccines Co-Targeting HER2/Neu and IGF1R Cancers cancer vaccines HER2/neu IGF1R muscle neoplasms DNA vaccines |
| title | Cancer Vaccines Co-Targeting HER2/Neu and IGF1R |
| title_full | Cancer Vaccines Co-Targeting HER2/Neu and IGF1R |
| title_fullStr | Cancer Vaccines Co-Targeting HER2/Neu and IGF1R |
| title_full_unstemmed | Cancer Vaccines Co-Targeting HER2/Neu and IGF1R |
| title_short | Cancer Vaccines Co-Targeting HER2/Neu and IGF1R |
| title_sort | cancer vaccines co targeting her2 neu and igf1r |
| topic | cancer vaccines HER2/neu IGF1R muscle neoplasms DNA vaccines |
| url | https://www.mdpi.com/2072-6694/11/4/517 |
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