TY - JOUR
T1 - Induction of T-cell memory by a dendritic cell vaccine
T2 - A computational model
AU - Pappalardo, Francesco
AU - Pennisi, Marzio
AU - Ricupito, Alessia
AU - Topputo, Francesco
AU - Bellone, Matteo
N1 - Funding Information:
Funding: ‘Metodi e Modelli Matematici della Teoria Cinetica per Sistemi Complessi’ (PRIN 2009 to F.P. and M.P.) (in part); Italian Association for Cancer Research, AIRC, Milan (to M.B.); the Ministry of Health, Rome (to M.B.); and the Ministry of University and Research, FIRB, Rome (to M.B.).
PY - 2014/7/1
Y1 - 2014/7/1
N2 - 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. Contact: Supplementary information: Supplementary data are available at Bioinformatics online.
AB - 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. Contact: Supplementary information: Supplementary data are available at Bioinformatics online.
UR - http://www.scopus.com/inward/record.url?scp=84903737191&partnerID=8YFLogxK
U2 - 10.1093/bioinformatics/btu059
DO - 10.1093/bioinformatics/btu059
M3 - Article
SN - 1367-4803
VL - 30
SP - 1884
EP - 1891
JO - Bioinformatics
JF - Bioinformatics
IS - 13
ER -