Tumorigenicity assessment of human cell-processed therapeutic products

Human pluripotent stem cells (hPSCs) are expected to be sources of various cell types used for cell therapy, although hPSCs are intrinsically tumorigenic and form teratomas in immunodeficient animals after transplant. Despite the urgent need, no detailed guideline for the assessment of tumorigenicity of human cell-processed therapeutic products (hCTPs) has been issued. Here we describe our consideration on tumorigenicity and related tests of hCTPs. The purposes of those tests for hPSC-based products are classified into three categories: 1) quality control of raw materials; 2) quality control of intermediate/final products; and 3) safety assessment of final products. Appropriate types of tests need to be selected, taking the purpose(s) into consideration. In contrast, human somatic (and somatic stem) cells are believed to have little tumorigenicity. Therefore, GMP-compliant quality control is essential to avoid contamination of somatic cell-derived products with tumorigenic cells. Compared with in vivo tumorigenicity tests, in vitro cell proliferation assays may be more useful and reasonable for detecting immortalized cells that have a growth advantage in somatic cell-based products. The results obtained from tumorigenicity and related tests for hCTPs should meet the criteria for decisions on product development, manufacturing processes, and clinical applications.