Armored CAR T cells enhance antitumor efficacy and overcome the tumor microenvironment Journal Article

Authors: Yeku, O. O.; Purdon, T. J.; Koneru, M.; Spriggs, D.; Brentjens, R. J.
Article Title: Armored CAR T cells enhance antitumor efficacy and overcome the tumor microenvironment
Abstract: Chimeric antigen receptor (CAR) T cell therapy has shown limited efficacy for the management of solid tumor malignancies. In ovarian cancer, this is in part due to an immunosuppressive cytokine and cellular tumor microenvironment which suppresses adoptively transferred T cells. We engineered an armored CAR T cell capable of constitutive secretion of IL-12, and delineate the mechanisms via which these CAR T cells overcome a hostile tumor microenvironment. In this report, we demonstrate enhanced proliferation, decreased apoptosis and increased cytotoxicity in the presence of immunosuppressive ascites. In vivo, we show enhanced expansion and CAR T cell antitumor efficacy, culminating in improvement in survival in a syngeneic model of ovarian peritoneal carcinomatosis. Armored CAR T cells mediated depletion of tumor associated macrophages and resisted endogenous PD-L1-induced inhibition. These findings highlight the role of the inhibitory microenvironment and how CAR T cells can be further engineered to maintain efficacy. © 2017 The Author(s).
Journal Title: Scientific Reports
Volume: 7
ISSN: 2045-2322
Publisher: Nature Publishing Group  
Date Published: 2017-09-05
Start Page: 10541
Language: English
DOI: 10.1038/s41598-017-10940-8
PROVIDER: scopus
PMCID: PMC5585170
PUBMED: 28874817
Notes: Article -- Export Date: 2 October 2017 -- Source: Scopus
Citation Impact
MSK Authors
  1. Renier J Brentjens
    275 Brentjens
  2. David R Spriggs
    325 Spriggs
  3. Mythili Koneru
    6 Koneru
  4. Terence John Purdon
    59 Purdon
  5. Oladapo Olumoroti Yeku
    16 Yeku