aAVC Drug Translational Unit

Despite advances in medicine and technology, cancer and infectious diseases continue to pose serious threats to humanity. Cancer immunotherapy has made remarkable progress not only through the development of immune checkpoint blockade therapies but also with advances in immune cell engineering technologies. With regard to infectious diseases, since the beginning of the 21st century, a series of severe infectious disease outbreaks—most notably the COVID-19 pandemic—have occurred, causing devastating impacts on human lives and social infrastructures worldwide.

The artificial Adjuvant Vector Cell (aAVC) Drug Discovery Translational Research (TR) Unit promotes the development of an aAVC-based drug discovery platform targeting cancer and infectious diseases as one of RIKEN’s proprietary modalities. aAVCs are a vaccine-based therapeutic system that targets dendritic cells in vivo. By triggering innate immune responses, this system induces adaptive immunity as well as immunological memory. In this unit, tumor-associated antigens or viral antigens  for which fundamental immunological data have been established are selected, and preparations are made for clinical studies using aAVC-tumor antigen (TA) or aAVC-viral antigen (VA) incorporating these antigens (Figure). Specifically, the aAVC Drug Discovery TR Unit conducts Chemistry, Manufacturing, and Control processes—including manufacturing procedures, quality control, and toxicological testing—to produce aAVC-TA or aAVC-VA for preclinical studies. Subsequently, safety and efficacy are evaluated through the preclinical studies. In addition, the unit not only supports the manufacture of aAVC-TA/VA in compliance with Good Manufacturing Practice standards but also engages in consultations and regulatory interactions with the Pharmaceuticals and Medical Devices Agency in preparation for clinical trials.

We have generated a next-generation vaccine, “aAVC-CoV-2,” which expresses the spike protein of SARS-CoV-2. Currently, we have generated aAVC‑CoV‑2 cells and conducted a series of preclinical evaluations, including safety pharmacology studies, efficacy studies, and antiviral activity assays under the framework of “Vaccine and New Modality Research and Development Program in the Japan Agency for Medical Research and Development. Further, based on the evidence obtained from preclinical studies, we have launched a Phase I clinical trial is underway targeting immunocompromised patients who do not achieve sufficient immunity with conventional COVID-19 vaccines in the current fiscal year. This trial is being conducted in collaboration with Kagawa University, the Institute of Medical Science at the University of Tokyo, Nippon Medical School, the Japanese Red Cross Medical Center, and the National Institute of Infectious Diseases. Because aAVCs constitute a platform in which antigens can be readily replaced, we aim to apply this strategy broadly to various cancers and infectious diseases.