Oncolytic Virotherapy Development for Breast Cancer
Breast Cancer (BC) is one of the most common types of cancer among women, ranking the second cause of cancer-related deaths, following lung cancer. Because of the severe toxicity associated with a long-term use of BC chemo and radiotherapy, it is extremely necessary to explore novel therapeutics. Besides, molecular heterogeneity at both intratumoral and intertumoral levels among BC subtypes seems to lead to a differential response to standard therapeutics. Nowadays, oncolytic viruses (OVs) have become one of the most promising treatment options for BC. A number of preclinical and clinical researches have exhibited that OVs are effective in treating BC, either as a single therapeutic agent or as a part of combination therapies. Based on Creative Biolabs' oncolytic virus development platform OncoVirapy™, coupled with our enhancing understanding of tumor oncology in BC, our scientists are capable of developing specific oncolytic virotherapy strategy followed by providing oncolytic virus construction and validation services to customers.
Breast Cancer Therapies
At present, surgery, chemotherapy and radiotherapy continue to be an important part of the standard therapy for BC. Hormone-based therapies take advantage of drugs that inhibit estrogen-and/or progesterone-mediated promotion of cancer cell growth. However, a main hurdle in using hormone-based therapies is that their effectiveness mostly bases on the expression of HRs on BC cells. Besides, a variety of immunotherapeutics are currently being tested for BC in several studies at both preclinical and clinical levels. There are several immune-stimulatory proteins being studied for therapeutic application in cancer patients, such as granulocyte colony-stimulating factor (GCSF), granulocyte monocyte colonystimulating factor (GMCSF), tumor necrosis factor (TNF), as well as a range of interleukins (ILs), for example, IL-2, IL-4, IL-12, IL-24. Currently, FDA has approved IFN-alpha2a, IFN-alpha2b and IL-2 to treat cancer. In addition, targeted therapies are novel treatment option for BC that refers to therapeutics directed at specific molecular targets, and they have shown a notable therapeutic efficacy in both preclinical and clinical studies.
Fig 1. A schematic diagram of how TILs in the TME are decreased to exert their effector functions by TLR ligands-reactivated DCs in the TME. (Suryawanshi, 2017)
Oncolytic Viruses for Breast Cancer
As a novel emerging therapeutic option for BC, OVs have many advantages over other therapeutics. Oncolytic virotherapy is on the basis of using viruses which enable to replicate in cancer cells, resulting in cell lysis and possibily expressing a range of therapeutic transgenes, such as immune-stimulatory factors, apoptotic inducers and prodrug activators. OVs constructed for the BC treatment mainly can be divided into two major groups: OVs naturally targeting indigenous defects in BC cells and engineered OVs. OVs have displayed an impressive therapeutic efficacy when utilized as a solo treatment agent in many preclinical studies. Therefore, a number of OVs are currently tested in clinical trials for safety and efficacy. For example, CVA21 is a none/wild-type Coxsackie virus A21, designed to treat solid tumors of BC; MVA-Brachyury-TRICOM is a vaccinia virus expressing brachyury and T cell costimulatory molecules which is in Phase I stage. In addition, OVs can also be applied as in combination therapies. It has exhibited that combination of low dose cyclophosphamide (CPA) with OVs induces an anticancer and anti-viral immune response in BC and other refractory cancers that increase overall survival.
With the rapid progress of novel therapeutic strategies in BC, oncolytic virus continues to hold promise as an effective treatment. Based on our advanced OncoVirapy™ platform, Creative Biolabs is confident in providing novel OVs and developing more efficient oncolytic virotherapy strategies for our customers.
Reference:
- Bartlett, D. L., (2013). "Oncolytic viruses as therapeutic cancer vaccines." Molecular cancer, 12(1), 103.
- Suryawanshi, (2017). "Oncolytic viruses: emerging options for the treatment of breast cancer." Medical Oncology, 34(3), 43.