Expression of Breast Cancer-Related Epitopes Targeting the IGF-1 Receptor in Chimeric Human Parvovirus B19 Virus-Like Particles
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Breast cancer is a worldwide health problem, and the complexity of the disease, as well as the lack of treatment specificity, generates an urgent need for developing prophylactic and therapeutic measures. Searching for novel epitope-based approaches able to induce tumour immunity, we designed virus-like particles (VLPs) derived from Human parvovirus B19 assembled of chimeric VP2 proteins displaying two epitopes from the insulin-like growth factor-1 receptor (IGF-1R). Here, we present the generation of two chimeric VP2s that retain the stability, solubility and conditions of purification and assembly of the native VP2. We generated versatile chimeric multiepitope anti-cancer vaccine candidates, which prevented and delayed tumour growth when used in a prophylactic scheme of 4 weekly immunizations prior to 4T1 cell inoculation in female BALB/c mice. The presence of specific antibodies against the displayed epitopes suggests their participation in the protective effect; in contrast, no significant proliferative T-cell responses were recorded following stimulation by specific epitopes. The results comprise an approach whereby fusing desired epitopes from cancer to the N-terminus of B19 VP2 protein can generate a library of chimeric VP2-desired epitopes for further assembly in a designed and personalized epitope delivery system.
KeywordsBreast cancer Vaccine VLPs Multiepitope IGF-1R
This work was supported by CONACYT CB283319 and UNAM PAPIIT IN223319. J.A. Salazar-González is a postdoctoral fellow and received a UNAM DGAPA scholarship. Thanks to Damaris Ilhuicatzi Alvarado for the technical support.
- 4.Farabaugh, S. M., Boone, D. N., & Lee, A. V. (2015). Role of IGF1R in breast cancer subtypes, stemness, and lineage differentiation. Frontiers in Endocrinology (Lausanne), 6, 59.Google Scholar
- 7.Stoeltzing, O., Liu, W., Reinmuth, N., Fan, F., Parikh, A. A., Bucana, C. D., et al. (2003). Regulation of hypoxia-inducible factor-1alpha, vascular endothelial growth factor, and angiogenesis by an insulin-like growth factor-I receptor autocrine loop in human pancreatic cancer. American Journal of Pathology, 163, 1001–1011.CrossRefGoogle Scholar
- 8.Bayrami, V., Keyhanfar, M., Mohabatkar, H., Mahdavi, M., & Moreau, V. (2016). In silico prediction of B cell epitopes of the extracellular domain of insulin-like growth factor-1 receptor. Molecular Biology Research Communications, 5(4), 201–214.Google Scholar
- 23.Bailey-Downs, L. C., Thorpe, J. E., Disch, B. C., Bastian, A., Hauser, P. J., Farasyn, T., et al. (2014). Development and characterization of a preclinical model of breast cancer lung micrometastatic to macrometastatic progression. PLoS ONE, 9(5), e98624. https://doi.org/10.1371/journal.pone.0098624.CrossRefGoogle Scholar
- 28.Cox, O. T., O’Shea, S., Tresse, E., Bustamante-Garrido, M., Kiran-Deevi, R., & O’Connor, R. (2015). IGF-1 Receptor and adhesion signaling: An important axis in determining cancer cell phenotype and therapy resistance. Frontiers in Endocrinology (Lausanne), 6, 106.Google Scholar