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

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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.