TY - JOUR T1 - Bispecific binder redirected lentiviral vector enables in vivo engineering of CAR-T cells JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1136/jitc-2021-002737 VL - 9 IS - 9 SP - e002737 AU - Justin T Huckaby AU - Elisa Landoni AU - Timothy M Jacobs AU - Barbara Savoldo AU - Gianpietro Dotti AU - Samuel K Lai Y1 - 2021/09/01 UR - http://jitc.bmj.com/content/9/9/e002737.abstract N2 - Background Chimeric antigen receptor (CAR) T cells have shown considerable promise as a personalized cellular immunotherapy against B cell malignancies. However, the complex and lengthy manufacturing processes involved in generating CAR T cell products ex vivo result in substantial production time delays and high costs. Furthermore, ex vivo expansion of T cells promotes cell differentiation that reduces their in vivo replicative capacity and longevity.Methods Here, to overcome these limitations, CAR-T cells are engineered directly in vivo by administering a lentivirus expressing a mutant Sindbis envelope, coupled with a bispecific antibody binder that redirects the virus to CD3+ human T cells.Results This redirected lentiviral system offers exceptional specificity and efficiency; a single dose of the virus delivered to immunodeficient mice engrafted with human peripheral blood mononuclear cells generates CD19-specific CAR-T cells that markedly control the growth of an aggressive pre-established xenograft B cell tumor.Conclusions These findings underscore in vivo engineering of CAR-T cells as a promising approach for personalized cancer immunotherapy.Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information. ER -