Chlorin e6-mediated photodynamic effect diminishes therapeutic potential of 5-aza-2'-deoxycytidine-based whole-tumour-cell vaccine in mice bearing squamous cell carcinoma SCCVII.

Abstract After years of setbacks, therapeutic cancer vaccines have become an alternative treatment option. Among the diversity of targeted tumour associated antigens (TAA), cancer–testis antigens (CTAs) are promising targets for cancer immunotherapy because they are highly immunogenic; meanwhile, they are expressed in human tumours of different histological origin but not in adult somatic tissues. Epigenetic modifications, such as DNA methylation, regulate CTAs expression both in normal and cancer cells. 5-Aza-2'-deoxycytidine (5-AZA-CdR), a DNA hypomethylating drug, induces the expression of CTAs in neoplastic cells. In these studies, we used 5-AZA-CdR-mediated up-regulation of CTAs and chlorin e6-mediated photodynamic effect in the production of a whole-tumour-cell vaccine against murine squamous cell carcinoma SCCVII in C3H/HeN mice. The results show that 5-AZA-CdR can be used to elevate levels of diverse CTAs in SCCVII cells. The 5-AZA-CdR-based vaccine, combined with the systemic administration of 5-AZA-CdR, delayed tumour growth. However, the treatment had no effect on survival in mice, most likely because of the toxicity of systemic treatment with 5-AZA-CdR. The photodynamic effect diminished therapeutic potential of 5-AZA-CdR-based vaccine. Chemo-immunotherapy with 5-AZA-CdR and therapeutic cancer vaccines may be an alternative approach to cancer therapy. However, further studies are needed to optimize treatment and vaccine preparation protocols.