Clinical Trials of Oncolytic Viruses in Breast Cancer

Abstract

Breast cancer is the second most common kind of cancer worldwide and oncolytic viruses may offer a new treatment approach. There are three different types of oncolytic viruses used in clinical trials; (i) oncolytic viruses with natural anti-neoplastic properties; (ii) oncolytic viruses designed for tumor-selective replication; (iii) oncolytic viruses modified to activate the immune system. Currently, fourteen different oncolytic viruses have been investigated in eighteen published clinical trials. These trials demonstrate that oncolytic viruses are well tolerated and safe for use in patients and display clinical activity. However, these trials mainly studied a small number of patients with different advanced tumors including some with breast cancer. Future trials should focus on breast cancer and investigate optimal routes of administration, occurrence of neutralizing antibodies, viral gene expression, combinations with other antineoplastic therapies, and identify subtypes that are particularly suitable for oncolytic virotherapy.

Keywords: breast cancer; clinical trials; oncolytic virus; review; virotherapy.

Figure 1

Four different ways used to engineer oncolytic viruses to selectively target tumor cells. Selective killing of tumor cells forms the first pillar of oncolytic virotherapy and requires specific targeting of cancer cells as a necessary pre-requisite for successful virotherapy. Although many naturally occurring viruses exhibit a natural preference for cancer cells, other viruses, need to be engineered to make them cancer specific.

Figure 2

Triggering an immune response through infection with oncolytic viruses. The infection of tumor cells with oncolytic viruses results in viral replication and subsequent cell lysis. The debris and new antigens that are released through cell lysis result in a stimulation of the immune system.

Figure 3

Clinical trials of oncolytic viruses in breast cancer. Oncolytic viruses selectively infect tumor tissue, undergo viral replication and cause tumor cell lysis. Currently, 14 different oncolytic viruses have been investigated in 18 published clinical trials. These oncolytic viruses fall into three different groups; (i) oncolytic viruses with natural anti-neoplastic properties; (ii) oncolytic viruses designed for tumor-selective replication; (iii) oncolytic viruses modified to activate the immune system. All published trials demonstrate that oncolytic viruses are well tolerated and safe for use in patients.