In silico modeling and in vivo efficacy of cancer-preventive vaccinations

Arianna Palladini, Giordano Nicoletti, Francesco Pappalardo, Annalisa Murgo, Valentina Grosso, Valeria Stivani, Marianna L. Ianzano, Agnese Antognoli, Stefania Croci, Lorena Landuzzi, Carla De Giovanni, Patrizia Nanni, Santo Motta, Pier Luigi Lollini

Research output: Contribution to journalArticle

Abstract

Cancer vaccine feasibility would benefit from reducing the number and duration of vaccinations without diminishing efficacy. However, the duration of in vivo studies and the huge number of possible variations in vaccination protocols have discouraged their optimization. In this study, we employed an established mouse model of preventive vaccination using HER-2/neu transgenic mice (BALB-neuT) to validate in silico - designed protocols that reduce the number of vaccinations and optimize efficacy. With biological training, the in silico model captured the overall in vivo behavior and highlighted certain critical issues. First, although vaccinations could be reduced in number without sacrificing efficacy, the intensity of early vaccinations was a key determinant of long-term tumor prevention needed for predictive utility in the model. Second, after vaccinations ended, older mice exhibited more rapid tumor onset and sharper decline in antibody levels than young mice, emphasizing immune aging as a key variable in models of vaccine protocols for elderly individuals. Long-term studies confirmed predictions of in silico modeling in which an immune plateau phase, once reached, could be maintained with a reduced number of vaccinations. Furthermore, that rapid priming in young mice is required for long-term antitumor protection, and that the accuracy of mathematical modeling of early immune responses is critical. Finally, that the design and modeling of cancer vaccines and vaccination protocols must take into account the progressive aging of the immune system, by striving to boost immune responses in elderly hosts. Our results show that an integrated in vivo - in silico approach could improve both mathematical and biological models of cancer immunoprevention.

Original languageEnglish
Pages (from-to)7755-7763
Number of pages9
JournalCancer Research
Volume70
Issue number20
DOIs
Publication statusPublished - Oct 15 2010

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Computer Simulation
Vaccination
Neoplasms
Cancer Vaccines
Biological Models
Transgenic Mice
Immune System
Theoretical Models
Vaccines
Antibodies

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Palladini, A., Nicoletti, G., Pappalardo, F., Murgo, A., Grosso, V., Stivani, V., ... Lollini, P. L. (2010). In silico modeling and in vivo efficacy of cancer-preventive vaccinations. Cancer Research, 70(20), 7755-7763. https://doi.org/10.1158/0008-5472.CAN-10-0701

In silico modeling and in vivo efficacy of cancer-preventive vaccinations. / Palladini, Arianna; Nicoletti, Giordano; Pappalardo, Francesco; Murgo, Annalisa; Grosso, Valentina; Stivani, Valeria; Ianzano, Marianna L.; Antognoli, Agnese; Croci, Stefania; Landuzzi, Lorena; De Giovanni, Carla; Nanni, Patrizia; Motta, Santo; Lollini, Pier Luigi.

In: Cancer Research, Vol. 70, No. 20, 15.10.2010, p. 7755-7763.

Research output: Contribution to journalArticle

Palladini, A, Nicoletti, G, Pappalardo, F, Murgo, A, Grosso, V, Stivani, V, Ianzano, ML, Antognoli, A, Croci, S, Landuzzi, L, De Giovanni, C, Nanni, P, Motta, S & Lollini, PL 2010, 'In silico modeling and in vivo efficacy of cancer-preventive vaccinations', Cancer Research, vol. 70, no. 20, pp. 7755-7763. https://doi.org/10.1158/0008-5472.CAN-10-0701
Palladini, Arianna ; Nicoletti, Giordano ; Pappalardo, Francesco ; Murgo, Annalisa ; Grosso, Valentina ; Stivani, Valeria ; Ianzano, Marianna L. ; Antognoli, Agnese ; Croci, Stefania ; Landuzzi, Lorena ; De Giovanni, Carla ; Nanni, Patrizia ; Motta, Santo ; Lollini, Pier Luigi. / In silico modeling and in vivo efficacy of cancer-preventive vaccinations. In: Cancer Research. 2010 ; Vol. 70, No. 20. pp. 7755-7763.
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