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.
Highlights
Tumor immunology compounds the complexity of oncology and of immunology
Cancer immunoprevention is a recent development of tumor immunology that aims at preventing tumor onset with immunologic means, in particular vaccines [6]
In silico design of cancer immunoprevention protocols The mammary glands of HER-2/neu transgenic BALB
Summary
Tumor immunology compounds the complexity of oncology and of immunology. The interaction creates a huge range of biological variables, what mathematicians would call a “large parameter space.” This makes it extremely difficult, if not utterly impossible, to exhaustively test all variables in a given biological experiment, in particular when working in vivo.Cancer immunoprevention is a recent development of tumor immunology that aims at preventing tumor onset with immunologic means, in particular vaccines [6]. The interaction creates a huge range of biological variables, what mathematicians would call a “large parameter space.”. This makes it extremely difficult, if not utterly impossible, to exhaustively test all variables in a given biological experiment, in particular when working in vivo. Cancer immunoprevention is a recent development of tumor immunology that aims at preventing tumor onset with immunologic means, in particular vaccines [6]. The brief explanation of the model included here is complemented by a more general description in the Supplementary material (Supplementary Text, Supplementary Fig. S1, and Supplementary Tables S1–S4)
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