Optimisation of anti-cancer peptide vaccines to preferentially elicit high-avidity T cells

Therapeutic cancer vaccines often do not substantially reduce tumour burden, despite stimulating anti tumour cytotoxic T lymphocytes (CTLs). Recent experiments have shown that the majority of vaccine elicited CTLs may be of low-avidity. Moreover, low-avidity CTLs, which are abundant, do not kill cancer cells and potentially inhibit the ability of high-avidity T cells to kill cancer cells. By modelling CTL selection using a system of ordinary differential equations, we show that the efficacy of the peptide vaccine may be improved by controlling its delivery and dosage to preferentially elicit high avidity CTLs. Our simulations predict that weekly, reduced doses of a vaccine may result in a greater than 90% reduction in cancer concentration. By contrast, a standard vaccine protocol such as a high-dose injection given every 2 weeks induces only a 65% reduction. Our model demonstrates a proof-of-concept approach to targeting immune responses for CTL selection, thereby offering a technique to potentially improve existing therapies. (C) 2019 Elsevier Ltd. All rights reserved.