CD4 and cancer: Engineered oncolytic constructs derived from herpes, adeno, vaccinia, pox or reoviruses have been evaluated in several phase I trials, showing feasibility of this approach with manageable side effects as well as humoral and genomic evidence cancer-specific immune activity such as cytotoxic CD8 (+) and CD4 (+) Th1 cell infiltration; decreased VEGF and tumor-promoting miRNA levels in tumor samples and upregulated IFN-gamma and IL 12 in blood samples [132,133,134].