Determination of the biodistribution of chimeric antigen receptor-modified T cells against CD19 in NSG mice

Along with the rising of the development of CAR-T therapy, the biodistribution and in vivo proliferation of CAR-T cells which are the basis of their effectiveness and safety, have aroused much attention. For IND application, the biodistribution characteristics of CAR-T cells are required to be determined using at least two methods (both quantitative and qualitative evaluation could be applicable) for a comprehensively understanding of their potential target organs/tissues. This chapter takes the CD19 targeted CAR-T cell as an example, to introduce the most commonly used experimental procedure and technical points of using tumor-bearing NSG mice to perform biodistribution research based on in vivo optical imaging, flow cytometry, histopathology/immunochemistry and real-time quantitative PCR. Although these protocols are not fully standardized and could be further optimized, the data obtained from these approaches has been accepted by U.S. Food and Drug Administration and China Food and Drug Administration.