Francesco Pappalardo1, Marzio Pennisi2, Alessia Ricupito1, Francesco Topputo1, Matteo Bellone1. 1. Department of Drug Science and Department of Mathematics and Computer Science, University of Catania, 95125 Catania, San Raffaele Scientific Institute and Università Vita Salute San Raffaele, 20132 Milan, Politecnico di Milano, 20133 Milano and San Raffaele Scientific Institute, 20132 Milan, Italy. 2. Department of Drug Science and Department of Mathematics and Computer Science, University of Catania, 95125 Catania, San Raffaele Scientific Institute and Università Vita Salute San Raffaele, 20132 Milan, Politecnico di Milano, 20133 Milano and San Raffaele Scientific Institute, 20132 Milan, ItalyDepartment of Drug Science and Department of Mathematics and Computer Science, University of Catania, 95125 Catania, San Raffaele Scientific Institute and Università Vita Salute San Raffaele, 20132 Milan, Politecnico di Milano, 20133 Milano and San Raffaele Scientific Institute, 20132 Milan, Italy.
Abstract
MOTIVATION: Although results from phase III clinical trials substantially support the use of prophylactic and therapeutic vaccines against cancer, what has yet to be defined is how many and how frequent boosts are needed to sustain a long-lasting and protecting memory T-cell response against tumor antigens. Common experience is that such preclinical tests require the sacrifice of a relatively large number of animals, and are particularly time- and money-consuming. RESULTS: As a first step to overcome these hurdles, we have developed an ordinary differential equation model that includes all relevant entities (such as activated cytotoxic T lymphocytes and memory T cells), and investigated the induction of immunological memory in the context of wild-type mice injected with a dendritic cell-based vaccine. We have simulated the biological behavior both in the presence and in the absence of memory T cells. Comparing results of ex vivo and in silico experiments, we show that the model is able to envisage the expansion and persistence of antigen-specific memory T cells. The model might be applicable to more complex vaccination schedules and substantially in any biological condition of prime-boosting. AVAILABILITY AND IMPLEMENTATION: The model is fully described in the article.
MOTIVATION: Although results from phase III clinical trials substantially support the use of prophylactic and therapeutic vaccines against cancer, what has yet to be defined is how many and how frequent boosts are needed to sustain a long-lasting and protecting memory T-cell response against tumor antigens. Common experience is that such preclinical tests require the sacrifice of a relatively large number of animals, and are particularly time- and money-consuming. RESULTS: As a first step to overcome these hurdles, we have developed an ordinary differential equation model that includes all relevant entities (such as activated cytotoxic T lymphocytes and memory T cells), and investigated the induction of immunological memory in the context of wild-type mice injected with a dendritic cell-based vaccine. We have simulated the biological behavior both in the presence and in the absence of memory T cells. Comparing results of ex vivo and in silico experiments, we show that the model is able to envisage the expansion and persistence of antigen-specific memory T cells. The model might be applicable to more complex vaccination schedules and substantially in any biological condition of prime-boosting. AVAILABILITY AND IMPLEMENTATION: The model is fully described in the article.
Authors: Mingyang Lu; Bin Huang; Samir M Hanash; José N Onuchic; Eshel Ben-Jacob Journal: Proc Natl Acad Sci U S A Date: 2014-09-22 Impact factor: 11.205