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Cancer Vaccines Co-Targeting HER2/Neu and IGF1R
- Source :
- Cancers, Vol 11, Iss 4, p 517 (2019), Cancers, Volume 11, Issue 4
- Publication Year :
- 2019
- Publisher :
- MDPI AG, 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.
- Subjects :
- DNA vaccine
0301 basic medicine
Cancer Research
Biology
medicine.disease_cause
lcsh:RC254-282
Article
HER2/neu
Receptor tyrosine kinase
DNA vaccination
DNA vaccines
03 medical and health sciences
0302 clinical medicine
IGF1R
medicine
Insulin-like growth factor 1 receptor
Transfection
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
body regions
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Cancer cell
biology.protein
Cancer research
muscle neoplasms
Antibody
cancer vaccine
Carcinogenesis
cancer vaccines
Subjects
Details
- Language :
- English
- ISSN :
- 20726694
- Volume :
- 11
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Cancers
- Accession number :
- edsair.doi.dedup.....bfa41f8f3a43cdac717a612dae0e8aca