Publication Date:
2018-11-29
Description:
CD19-specific Chimeric Antigen Receptor (CTL019)-engineered T-cells provide a breakthrough for personalized cancer therapy. An anti-CD19 CAR gene with 41BB costimulatory domain is delivered into patient T-cells ex vivo using a lentiviral vector, expanded in culture and then reinfused into patients. While dramatically successful for some treatment-refractory cancers, a significant proportion of patients do not experience therapeutic levels of CAR T cell expansion - thus it is important to investigate factors driving successful expansion in responders in more detail. Here we have analyzed sites of lentiviral vector integration in CAR T cells from trials to ALL and CLL, comparing successful and unsuccessful therapy in longitudinal data sets for 40 subjects. The location of each integrated vector marks a cell lineage uniquely allowing the fate mapping of individual CAR-engineered T cells in the infusion product and after adoptive transfer. We found that 81.4% of integrations had occurred in annotated transcription units which is consistent with previous reports for lentiviral vector integration sites. Relatively larger and more diverse populations of CAR-modified T-cells were associated with improved outcome (Chao1 index, p=0.043). Population sizes were also significantly more diverse in the infusion product compared with day 28 post-infusion, and more diverse at this time point when comparing responders with non-responders, or even partial responders with non-responders (p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine