One type of cancer immunotherapy, called oncolytic viral therapy, works by infecting cancer cells with a specific virus. Some oncolytic viruses occur naturally, while others result from specialized engineering performed in a laboratory. Oncolytic viruses replicate within cancer cells, proving a mechanism to kill cancer cells without damaging healthy cells. The use of oncolytic viral therapy for cancer treatment is rapidly growing. Currently, clinicaltrials.gov lists over 100 ongoing or recently completed Clinical Trials testing the efficacy of various oncolytic viruses.
A research team recently presented promising data emerging from one multicenter Clinical Trial at the European Society for Medical Oncology Annual Meeting. The trial tests a drug called RP2, an oncolytic virus developed from the herpes simplex virus type 1 (HSV-1). In part, the RP2 oncolytic virus is engineered to inhibit CLTA-4 signaling in an effort to improve the ability of T cells to kill cancer cells. The researchers tested RP2 both as a monotherapy and in combination with nivolumab, an immune checkpoint inhibitor targeting PD-1. Patients enrolled in the trial received eight doses of RP2 plus nivolumab administered every other week for four months and then monthly for 20 months.
Nine patients received RP2 monotherapy, of which three exhibited responses lasting at least 15 months. Twenty patients received RP2 in combination with nivolumab. RP1 plus nivolumab demonstrated significant responses in various cancer types, including cutaneous melanoma (44.4%), uveal melanoma (25%), and head and neck carcinoma (33%). Overall, seven out of 20 patients who responded to the therapy had previously failed treatment with PD-1 inhibition. Additionally, six of the seven responders had maintained durable responses for over 425 days at the time of the presentation.
Many studies indicate that immune cell infiltration to the tumor correlates to response to immune checkpoint inhibitors. In order to evaluate the immune cell profile of the responding tumors, researchers performed immunohistochemistry (IHC). The IHC analysis revealed that the treatment increased infiltration of CD8 T cells, also known as cytotoxic T lymphocytes (CTLs), the subset of immune cells responsible for killing cancer cells. Further, the researchers evaluated the ratio of CD8 T cells to immunosuppressive cells positive for Foxp3, known as regulatory T cells. The analysis showed that treatment correlated to a favorable balance of CD8/Foxp3 cells.
The researchers conclude that RP2, combined with nivolumab, generated durable systemic responses in patients with advanced cancers who have failed prior treatment options. Although early, this data suggests a new potential treatment option for patients without other therapeutic options.