Abstract
Adoptive cellular therapy (ACT) is one of the most advanced immunotherapies, that has demonstrated the highest objective response rates in patients with haematological cancers. The success of ACT in solid tumours, however, is limited. Previous studies by our group showed that a p53 isoform, Δ133p53, has oncogenic properties, promoting cancer progression and is associated with a poor prognosis in human cancers. Based on this, we wish to determine how ∆133p53 could affect the efficacy of ACT using a mouse model of melanoma. In light of prior research, we hypothesize that the expression of the mouse analogue ∆122p53 by the tumour cells could negatively affect the ACT-mediated anti-tumour immune responses.
To test our hypothesis, we genetically modified B16-OVA melanoma cells to stably express either, Δ122p53 or an empty vector (EV), then subcutaneously implanted into naïve mice. The mice were then treated with ACT to determine the therapeutic responses.
Consistent with previous findings, Δ122p53 tumours grew faster and their size was significantly bigger than the EV-expressing tumours on the day of treatment. However, the median survival and tumour growth rate following treatment was very similar in Δ122p53-ACT and EV-ACT treated groups. These results suggest that, although Δ122p53 promotes tumour growth, it does not suppress ACT-mediated anti-tumour immune responses and in fact may stimulate a sustained anti-tumour immune response.
This research has the potential to determine the effect of ∆133p53 on immunotherapies and may be translated to clinical investigations to improve treatment outcomes for solid cancers.