Cancer stands as the primary cause of death among the top ten mortality factors in Taiwan, with its incidence and mortality rates escalating annually. It is imperative to continually advance and enhance cancer treatments in response. Under The National Science and Technology Committee (NSTC) support 「Lactate-activated hypoxia-responsive Carrier for viral RNA interference and regulated Tumor-Associated Macrophage for immunotherapy」program，The Dr. Zi-Xian Liao and her teams are dedicated to addressing these issues by enhancing virus targeting efficiency and developing various systems for controlled virus release. By leveraging the tumor microenvironment's characteristics, they aim to establish a treatment platform for non-small cell lung cancer (NSCLC) that enhances the efficacy of viral therapy. This project is supported by the National Science Council's long-term special research project.
Widely utilized cancer treatment methods encompass surgical resection, radiation therapy, chemotherapy, immunotherapy, and virotherapy. Virotherapy, in particular, offers a gentle and safe approach that employs viruses possessing tumor-targeting and tumor-destroying properties. This treatment strategy improves both the survival rate and quality of life for patients. While oncolytic virotherapy received clinical approval in 2015, and the delivery of recombinant adeno-associated virus (rAAV) was licensed in 2017, the limited success of viruses reaching the intended target site remains a challenge. Despite the US Food and Drug Administration (FDA) allowing higher doses, most viruses accumulate in the liver, resulting in ineffective treatment.
To enhance the application of virotherapy and improve treatment efficiency for NSCLC, Dr. Liao and her team have developed various mechanized vector delivery systems in conjunction with virus therapy. These systems aim to amplify the therapeutic efficacy and include magnetic viruses, photodynamic magnetic viruses, and nanoparticles-modified viruses sensitive to the tumor microenvironment. These systems not only enhance the efficiency and precision of vector delivery through the bloodstream, ensuring accurate release at tumor sites, but also minimize side effects resulting from non-targeted delivery. The magnetic virus functions as an immediate tracking tool for viruses.
To expand the applicability of these development systems to different tumor treatment platforms, the team conducts diverse nano-modifications on the systems. They integrate immune checkpoint inhibitors (ICIs) approved by the US FDA to modulate the immune system within the tumor microenvironment and treat liver cancer. By transforming tumor-promoting macrophages (TAM) into tumor-inhibiting ones, these systems impede tumor growth and stimulate immune responses to recruit more tumor-suppressing immune cells. The accumulation of macrophages enhances the immunosuppressive effect around the tumor while inhibiting the proliferation of liver cancer cells.
The various modified viral systems not only find applications in diverse tumor treatments but also synergize with photodynamic therapy, immunotherapy, and other combination therapies. These approaches augment healing efficiency, regulate constructive immunity, enhance the effectiveness of tumor growth inhibition, and reinforce the integration of viruses, immunity, and nanotechnology in cancer treatment. Furthermore, the use of magnetic viruses holds promise in overcoming traditional challenges associated with tracking virus distribution within the body. These advancements prove beneficial for the interdisciplinary biomedical industry and the advancement of virotherapy.
Media Contact
Tze-Hao Chang
Program Manager
Department of Engineering and Technologies
National Science and Technology Council
TEL: +886-2-27377371
E-mail: thchang@nstc.gov.tw
