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.

Induction of T-cell Memory by a Dendritic Cell Vaccine: a Computational Model

TOPPUTO, FRANCESCO;
2014-01-01

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. Contact: Supplementary information: Supplementary data are available at Bioinformatics online.
2014
File in questo prodotto:
File Dimensione Formato  
PAPPF01-14.pdf

accesso aperto

: Publisher’s version
Dimensione 483.75 kB
Formato Adobe PDF
483.75 kB Adobe PDF Visualizza/Apri
Induction of T-cell memory by a dendritic cell vaccine_11311-787321_Topputo.pdf

accesso aperto

: Post-Print (DRAFT o Author’s Accepted Manuscript-AAM)
Dimensione 474.44 kB
Formato Adobe PDF
474.44 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11311/787321
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 33
  • ???jsp.display-item.citation.isi??? 28
social impact