RT Journal Article
SR Electronic
T1 Bispecific binder redirected lentiviral vector enables in vivo engineering of CAR-T cells
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP e002737
DO 10.1136/jitc-2021-002737
VO 9
IS 9
A1 Justin T Huckaby
A1 Elisa Landoni
A1 Timothy M Jacobs
A1 Barbara Savoldo
A1 Gianpietro Dotti
A1 Samuel K Lai
YR 2021
UL http://jitc.bmj.com/content/9/9/e002737.abstract
AB 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.