Oncolytic Virotherapy Development for Gynecologic Malignancies
Gynecologic cancer is one of the most leading causes of cancer death among women worldwide. A number of women with early-stage disease are cured with a combination of surgery, radiation, and chemotherapy. Nevertheless, the malignancies are usually diagnosed at advanced stages, especially ovarian cancer, and many patients relapse despite suitable management. Thus, the treatment of gynecologic cancers remains to be a big therapeutic challenge, and there is an unmet clinical requirement for new therapies. At present, the strategies to treat gynecologic malignancies mainly include surgery, radiation, chemotherapy and immunotherapy. In the past years, the capacity of cancer cells to evade immune destruction has considered to be one of the hallmarks of cancer. Clinical trials have exhibited great efficacy for various immunotherapeutic approaches, such as the use of tumor-targeting antibodies, enhancement of tumor antigen presentation, and the targeting of immunosuppressive mechanisms. Recently, oncolytic viruses (OVs) selectively infecting and replicating in cancer cells have attracted considerable attention as promising anti-cancer agents. Based on our well established oncolytic virus development platform OncoVirapy™, Creative Biolabs is confident in developing specific oncolytic virotherapy strategies, and providing oncolytic virus construction and validation services for the treatment of gynecologic malignancies.
Ovarian Cancer
As is initially felt that epithelial ovarian cancer would not respond well to immunotherapy, however, studies have inhibited a key role for the immune system in the control of epithelial ovarian cancer cell growth. Generally, there are two mostly used strategies to treat ovarian cancer: therapies to enhance tumor antigen recognition and therapies to enhance t-cell activation. Therapeutic methods that aim to improve tumor recognition by the immune system enable to be collectively grouped into vaccines and innate immune activators, such as TLR agonists, type I interferon (IFN), and oncolytic viruses. Therapeutic methods aiming to improve the T-cell activation are controlled by a number of factors, such as cytokines and a range of immune stimulatory and inhibitory receptors.
Cervical Cancer
Nowadays, a variety of immunotherapeutic approaches have been studied in cervical cancer, especially in light of its association with human papillomavirus (HPV). The genotypes HPV-16 and HPV-18 account for most of cases of invasive cervical cancer. The HPV E6 and E7 oncoproteins are expressed intracellularly in HPV-associated cancers, which stand for a target for therapeutic vaccines. Moreover, many different types of vaccines have been developed for use in treating cervical cancer, such as protein and peptide vaccines, DC vaccines, live vector–based vaccines, as well as nucleic acid–based vaccines.
Endometrial Cancer
On account of the limited understanding of the interplay between the immune system and endometrial cancer, only few of immunotherapeutic methods have been explored, one of which is DC vaccines, and a number of studies have explored the use of DC vaccines in treating uterine cancer. The other important method is immune checkpoint blockade. However, the use of immune checkpoint blockade has not yet been broadly explored in endometrial cancer.
Fig 2. Schematic diagram of the improved T cell priming in oncolytic virotherapy. (Woller, N., 2014)
Oncolytic Viruses (OVs) for Gynecologic Malignancies
Due to their special characteristics that selectively infect or replicate in cancer cells, OV is considered to be a promising anti-cancer agent. Compared to common gene therapy, in which replication-incompetent viral vectors are used for therapeutic gene delivery, OVs are replication-competent agents which selectively kill cancer cells but spare normal cells. Moreover, infection with OVs results in the release of progeny virions that spread throughout the tumor. However, typical viral vectors do not spread and are thus unable to transfer their therapeutic gene into the majority of tumor cells. To date, there are a variety of OVs in clinical trials for gynecological cancers, such as ONYX-015 (adenovirus, treatment of patients with recurrent OC), H101 (adenovirus, treatment of treatment of malignant ascites), Measles vaccine virus-CEA (treatment of patients with recurrent OC), as well as Mumps virus (treatment of advanced gynecological cancers).
Our OncoVirapy™ platform offers full-scale OV construction and validation services to meet our clients' project development in the field of gynecologic malignancies treatment. Flexible as we would have been, our services can be customized to fit your project needs. We always devote ourselves to providing you with the best and professional OV services. Please contact us for more information and a detailed quote.
Reference:
- Hartkopf, A. D., (2011). "Oncolytic virotherapy of gynecologic malignancies." Gynecologic oncology, 120(2), 302-310.
- Woller, N., (2014). "Oncolytic viruses as anticancer vaccines." Frontiers in oncology, 4.