 The study aims to develop an innovative gene modification therapy for refractory or recurrent B-lineage hematologic malignancies, using anti-CD19 chimeric antigen receptor, CAR, and herpes simplex virus thymidine kinase, HSVSR39TK, suicide gene. The study developed high-titer third-generation self-inactivating lentival constructs to deliver a second generation, CD19-specific CAR and HSVSR39TK to provide a suicide gene, which allows ablation of gene-modified cells if necessary. Human HSC were transduced with such lentival vectors and evaluated for function of both CAR and HSVSR39TK. The study found satisfactory transduction efficiency, and the addition of the suicide gene did not impair car expression or antigen-specific cytotoxicity. NSG mice transplanted with gene-modified human HSC showed CAR expression not significantly different between transduced cells with without HSVSR39TK, an expression of anti-CD19 CAR conferred anti-chumor survival advantage. Treatment with Gansiklovia led to significant ablation of gene-modified cells in mouse tissues. The study suggests that a portion of the collected HSC could be modified to express the CD19-specific CAR and give rise to a persistent, multi-cell lineage, HLA-independent immunotherapy, enhancing the graft versus malignancy activity. This article was authored by Sarah M. Larson, Laurel C. Truskett, Tsuting Chu, and others. We are article.tv, links in the description below.