遺伝子治療用製品の生体内分布と安全性・有効性の評価法

抄録

In recent years, gene therapy has been developed for various intractable diseases, and some have been approved as gene therapy products based on the satisfactory results of their safety and efficacy. In particular, vectors derived from adeno-associated virus with modified virus capsids have allowed an intravenous administration and expanded target diseases in in vivo gene therapy. In addition, chimeric antigen receptor T cell (CAR-T) therapy effective currently for hematopoietic malignancies is being developed for solid tumors. On the other hand, safety and efficacy including bio-distribution of such gene therapy products is usually evaluated by molecular biological methods. Thus, the products do not fit into the PK/PD concept used in conventional drug development and it is required to set up a new evaluation system such as droplet digital PCR (ddPCR) capable of single cell analysis and the next-generation sequencer (NGS) capable of comprehensive genome analysis, although the challenge is how to guarantee the reliability of the results. 

In this symposium, I would like to introduce you a safety and efficacy evaluation system adopted in our Center using clinical specimens obtained from patients who have actually treated with in vivo or ex vivo gene therapy and discuss the ideal form of PK/PD tests for gene therapy products.