Journal
JOURNAL FOR IMMUNOTHERAPY OF CANCER
Volume 9, Issue 9, Pages -Publisher
BMJ PUBLISHING GROUP
DOI: 10.1136/jitc-2021-002737
Keywords
immunotherapy; cell engineering; receptors; chimeric antigen; antibody specificity
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Funding
- National Science Foundation Graduate Research Fellowship Program [DGE-1650116]
- NIDCR of the National Institutes of Health [F32DE026683]
- National Institutes of Health [5-R01-CA193140]
- David and Lucile Packard Foundation [2013-39274]
- Eshelman Institute for Innovation
- Dissertation Completion Fellowship from The Graduate School at UNC-Chapel Hill
- Eshelman School of Pharmacy and Lineberger Comprehensive Cancer Center at UNC-Chapel Hill
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The study demonstrates the in vivo engineering of CAR-T cells using a redirected lentiviral system that offers exceptional specificity and efficiency in controlling the growth of aggressive B cell tumors, highlighting the promising approach for personalized cancer immunotherapy.
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.
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