Genome-wide profiling of retroviral DNA integration and its effect on clinical pre-infusion CAR T-cell products

Lipei Shao, Rongye Shi, Yingdong Zhao, Hui Liu, Alexander Lu, Jinxia Ma, Yihua Cai, Tatyana Fuksenko, Alejandra Pelayo, Nirali N. Shah, James N. Kochenderfer, Scott M. Norberg, Christian Hinrichs, Steven L. Highfill, Robert P Somerville, Sandhya R. Panch, Ping Jin & David F. Stroncek
Abstract Background Clinical CAR T-cell therapy using integrating vector systems represents a promising approach for the treatment of hematological malignancies. Lentiviral and γ-retroviral vectors are the most commonly used vectors in the manufacturing process. However, the integration pattern of these viral vectors and subsequent effect on CAR T-cell products is still unclear. Methods We used a modified viral integration sites analysis (VISA) pipeline to evaluate viral integration events around the whole genome in pre-infusion CAR...
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