Subcutaneous injections of tumour cell lines into mice are used to test cancer vaccines for the treatment of colorectal cancer (CRC). We determined the baseline immune response to subcutaneous injection of the adenocarcinoma colorectal cell line, CT26, and compared it to injection with the melanoma cell line, B16-OVA. We characterised immune cell differences between these two commonly used tumour models.
The systemic immune response to CT26 tumours was characterised by a higher frequency of dendritic cells, a lower frequency of T cells, and twice the proportion of CD4+ to CD8+ T cells, compared to mice given B16-OVA tumours (n = 14-15, Mann Whitney, P = 0.0016, P = 0.0366, P = 0.0001, respectively). The intra-tumoural immune response to CT26 tumours consisted of a reduced macrophage and T cell infiltrate compared to B16-OVA tumours (n = 14, Mann Whitney, P = 0.0233, P = 0.0185, respectively). We also optimised a murine surgical model of CRC using an intracaecal injection. We compared this colon model to the subcutaneous model to see if there were differences in the immune response.
To determine if the immune response to CRC could be modulated with a cancer vaccine, mice were vaccinated with chitosan gel alone, gel and the endgoneous tumour peptide AH1, or PBS for the control. Mice were then challenged either subcutaenously or intracaecally with CT26. Additional experiments were carried out using the vaccine therapeutically. The chitosan gel vaccine provided protection against tumour growth in both subcutaneous and intracaecal models and was correlated with an increase in antigen specific T cells. These cells have also been shown to be important in human CRC. This work will help link animal models and human data, and help translate cancer therapeutics into treatments for human patients.