Journal title
Journal of the Royal Society Interface
DOI
10.1098/rsif.2018.0041
Issue
140
Volume
15
Last updated
2024-04-11T19:31:48.143+01:00
Abstract
Tumour immunotherapy is dependent upon activation and expansion of tumour targetting immune cells, known as Cytotoxic T-Lymphocytes (CTLs). Cancer vaccines developed in the past have had limited success and the mechanisms resulting in failure are not well characterised. To elucidate these mechanisms, we developed a human parameterised, in silico, agent based model of vaccination-driven CTL activation within a clinical short-peptide vaccination context. The simulations predict a sharp transition in the probability of CTL activation, which occurs with variation in the separation rate (or off-rate) of tumour specific immune-response inducing peptides (cognate antigen) from the major histocompatibility class I receptors (MHC-I) of dendritic cells originally at the vaccination site. For peptides with MHC-I off-rates beyond this transition, it is predicted that no vaccination strategy will lead to successful expansion of CTLs. For slower off-rates, below the transition, the probability of CTL activation becomes sensitive to the numbers of dendritic cells and T cells that interact subsequent to dendritic cell migration to the draining lymph node of the vaccination site. Thus, the off-rate is a key determinant of vaccine design.
Symplectic ID
831339
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Publication type
Journal Article
Publication date
14 Mar 2018