Safety and stability of retrovirally transduced chimeric antigen receptor T cells

Evaluation of: Scholler J, Brady TL, Binder-Scholl G et al. Decade-long safety and function of retroviral-modified chimeric antigen receptor T cells. Sci. Transl Med. 4(132), 132-153 (2012). Adoptive cellular therapy with genetically engineered T cells is predicated on generating effective and persisting T-cell-mediated immunity. Gammaretroviral vector-mediated gene transfer in T cells is the technological basis for promising therapy in both HIV and cancer. Because of concerns over delayed adverse events caused by persisting retroviral vector-engineered cells, the US FDA mandates long-term follow-up of clinical trials. Scholler et al. report FDA-mandated safety data and demonstrate that retrovirally transduced T cells persist in the blood of patients for more than a decade after treatment. These persisting T cells proliferated ex vivo in the presence of antigens and showed no evidence of either insertional oncogenesis or clonal expansion in 11 subjects followed for up to 11 years, supporting the long-term safety and persistence of retrovirally transduced T cells.