Towards Novel Gene and Cell Therapy Approaches for Cervical Cancer

SIMPLE SUMMARY: Current treatments for cervical cancer patients include surgery, radiation and chemotherapy, which may be combined. Unfortunately, it is not always possible to remove all of the cancer and some cancer cells may be resistant to radio-/chemotherapy. This can result in lack of disease control or cancer relapse after initial response to therapy. Furthermore, metastasis of the tumor cells presents another difficult therapeutic challenge. The advent of novel immunotherapies, including monoclonal antibodies and genetically modified immune cells, that augment anti-cancer activity of immune cells holds great promise to improve cervical cancer patient survival. ABSTRACT: Cervical cancer is one of the most common malignancies in women, and the majority of cases are caused by infection with high-risk human papilloma virus (HPV) subtypes. Despite effective preventative measures, such as vaccinations against HPV, over 300,000 women die world-wide from cervical cancer each year. Once cervical cancer is diagnosed, treatment may consist of radial hysterectomy, or chemotherapy and radiotherapy, or a combination of therapies dependent upon the disease stage. Unfortunately, overall prognosis for patients with metastatic or recurrent disease remains poor. In these cases, immunotherapies may be useful based on promising preclinical work, some of which has been successfully translated to the clinic. For example, approaches using monoclonal antibodies directed against surface proteins important for control of immune checkpoints (i.e., immune checkpoint inhibitors) were shown to improve outcome in many cancer settings, including cervical cancer. Additionally, initial clinical studies showed that application of cytotoxic immune cells modified to express chimeric antigen receptors (CAR) or T cell receptors (TCR) for better recognition and elimination of tumor cells may be useful to control cervical cancer. This review explores these important topics, including strengths and limitations of standard and developing approaches, and how some novel treatment strategies may be optimally used to offer the best possible treatment for cervical cancer patients.