Engineered tumor-targeted T cells mediate enhanced anti-tumor efficacy both directly and through activation of the endogenous immune system Journal Article

   

Authors:	Avanzi, M. P.; Yeku, O.; Li, X.; Wijewarnasuriya, D. P.; van Leeuwen, D. G.; Cheung, K.; Park, H.; Purdon, T. J.; Daniyan, A. F.; Spitzer, M. H.; Brentjens, R. J.
Article Title:	Engineered tumor-targeted T cells mediate enhanced anti-tumor efficacy both directly and through activation of the endogenous immune system
Abstract:	Chimeric antigen receptor (CAR) T cell therapy has proven clinically beneficial against B cell acute lymphoblastic leukemia and non-Hodgkin's lymphoma. However, suboptimal clinical outcomes have been associated with decreased expansion and persistence of adoptively transferred CAR T cells, antigen-negative relapses, and impairment by an immunosuppressive tumor microenvironment. Improvements in CAR T cell design are required to enhance clinical efficacy, as well as broaden the applicability of this technology. Here, we demonstrate that interleukin-18 (IL-18)-secreting CAR T cells exhibit enhanced in vivo expansion and persistence and significantly increase long-term survival in syngeneic mouse models of both hematological and solid malignancies. In addition, we demonstrate that IL-18-secreting CAR T cells are capable of modulating the tumor microenvironment, as well as enhancing an effective endogenous anti-tumor immune response. IL-18-secreting CAR T cells represent a promising strategy to enhance the clinical outcomes of adoptive T cell therapy. Avanzi et al. generate CAR T cells that secrete IL-18 and show improved activity in syngeneic hematologic and solid tumor models without prior preconditioning. They further show enhanced recruitment and anti-tumor activity of endogenous T cells. © 2018 The Authors
Keywords:	ovarian cancer; chimeric antigen receptor; adoptive transfer; muc16; interleukin-18; il-18; car t cell; armored car; b-all
Journal Title:	Cell Reports
Volume:	23
Issue:	7
ISSN:	2211-1247
Publisher:	Cell Press
Date Published:	2018-05-15
Start Page:	2130
End Page:	2141
Language:	English
DOI:	10.1016/j.celrep.2018.04.051
PROVIDER:	scopus
PUBMED:	29768210
PMCID:	PMC5986286
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85046674047&doi=10.1016%2fj.celrep.2018.04.051&partnerID=40&md5=f1a9560def69d6c0ef4e179a5f173e3f
Notes:	Article -- Export Date: 1 June 2018 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/124946