Vitamin D as a Primer for Oncolytic Viral Therapy in Colon Cancer Models

Abstract

Oncolytic viroimmunotherapy is an exciting modality that can offer lasting anti-tumor immunity for aggressive malignancies like colon cancer. The impact of oncolytic viruses may be extended by combining them with agents to prime a tumor for viral susceptibility. This study investigates vitamin D analogue as an adjunct to oncolytic viral therapy for colon cancer. While vitamin D (VD) has historically been viewed as anti-viral, our in vitro investigations using human colon cancer cell lines showed that VD does not directly inhibit replication of recombinant chimeric poxvirus CF33. VD did restrict growth in HT29 but not HCT116 human colon cancer cells. In vivo investigations using HCT116 and HT29 xenograft models of colon cancer demonstrated that a VD analogue, calcipotriol, was additive with CF33-based viral therapy in VD-responsive HT29 but not in HCT116 tumors. Analyses of RNA-sequencing and gene expression data demonstrated a downregulation in the Jak-STAT signaling pathway with the addition of VD to viral therapy in HT29 models suggesting that the anti-inflammatory properties of VD may enhance the effects of viral therapy in some models. In conclusion, VD may prime oncolytic viral therapy in certain colon cancers.

Priming stroma with a vitamin D analog to optimize viroimmunotherapy for pancreatic cancer

“… 17 In a similar set of experiments using colon cancer models, we demonstrated decreased inflammatory signaling following Cal pretreatment. 23 Currently, we are attempting to elucidate the immune-inflammatory axis before and after virus infection in more clinically relevant models.…”

“… 19 , 20 , 21 However, we have shown that viruses derived from CF33 replicate unhindered in the presence of Cal. 22 , 23 Given that treatment with Cal activates VDR in PDAC stroma and enhances the delivery of chemotherapy, 17 we asked whether this same stromal reprogramming could enhance OV delivery and immunogenicity ( Figure 1 ). Here, we used the CF33 platform to address the hypothesis that Cal primes PDAC stroma to enhance OV delivery, tumor destruction, and immune cell recruitment and activation against pancreatic cancer.…”

A new strategy for treating colorectal cancer: Regulating the influence of intestinal flora and oncolytic virus on interferon

“…On the one hand, OVs can naturally identify cancer cells by the characteristics of cancer cell biomarkers 97 or the properties of gene and protein expression. 98 On the other hand, genetic engineering has further enhanced the specificity of OVs. Virus infection can cause cancer cells to produce soluble antigens and danger signals, release IFN, and improve the TME.…”