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.
Highlights
One in eight women will be diagnosed with breast cancer in their life, and breast cancer is the most common kind of cancer in the United States
As Herpes simplex Virus (HSV) infections and seropositivity are common in the population it is important to note that an effective tumor treatment with OncoVEXGM-CSF is still achievable when applied intratumorally; as a result of this route of application any local preformed anti-Herpes simplex virus type 1 (HSV-1) immune response is overwhelmed by the huge number of locally applied infectious viral particles
We have reviewed the different viruses that have been investigated in published clinical trials for the treatment of breast cancer (Figure 1 and Table 1)
Summary
One in eight women will be diagnosed with breast cancer in their life, and breast cancer is the most common kind of cancer in the United States. New strategies are needed to improve the efficacy of immunotherapy in breast cancer, which is not considered a highly immunogenic (i.e. hot) tumor compared to other entities such as melanoma or non-small cell lung cancer [22] Novel treatment agents such as immune checkpoint inhibitors are an important milestone in response to the desperate search for novel therapeutic agents for breast cancer. Herpes simplex virus type 1 (HSV-1) was the first oncolytic virus to be genetically modified by creating a thymidine kinase-negative mutant of HSV-1 [32] Many studies followed this development resulting in a variety of viruses which were found to exhibit tumor-selective replication [31, 33]. Oncolytic viruses are promising agents for the treatment of cancer because they selectively infect and destroy cancerous tissues without harming normal tissues [9] They offer an attractive combination of tumor-specific cell lysis and immune stimulation. We have searched unpublished clinical trials found on Clinical Trial Research: Trial Trove using oncology, breast as keywords for disease and lytic virus/virus, lytic as the keywords for therapeutic class
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