• Skip to primary navigation
  • Skip to main content
SRI logo
  • About
    • Press room
    • Our history
  • Expertise
    • Advanced imaging systems
    • Artificial intelligence
    • Biomedical R&D services
    • Biomedical sciences
    • Computer vision
    • Cyber & formal methods
    • Education and learning
    • Innovation strategy and policy
    • National security
    • Ocean & space
    • Quantum
    • QED-C
    • Robotics, sensors & devices
    • Speech & natural language
    • Video test & measurement
  • Ventures
  • NSIC
  • Careers
  • Contact
  • 日本支社
Search
Close
Biomedical sciences publications August 1, 2014 Article

ICOS-Based Chimeric Antigen Receptors Program Bipolar Th17/Th1 Cells

Abstract

With the notable exception of B-cell malignancies, the efficacy of chimeric antigen receptor (CAR) T cells has been limited, and CAR T cells have not been shown to expand and persist in patients with nonlymphoid tumors. Here we demonstrate that redirection of primary human T cells with a CAR containing the inducible costimulator (ICOS) intracellular domain generates tumor-specific IL-17-producing effector cells that show enhanced persistence. Compared with CARs containing the CD3ζ chain alone, or in tandem with the CD28 or the 4-1BB intracellular domains, ICOS signaling increased IL-17A, IL-17F, and IL-22 following antigen recognition. In addition, T cells redirected with an ICOS-based CAR maintained a core molecular signature characteristic of TH17 cells and expressed higher levels of RORC, CD161, IL1R-1, and NCS1. Of note, ICOS signaling also induced the expression of IFN-γ and T-bet, consistent with a TH17/TH1 bipolarization. When transferred into mice with established tumors, TH17 cells that were redirected with ICOS-based CARs mediated efficient antitumor responses and showed enhanced persistence compared with CD28- or 4-1BB-based CAR T cells. Thus, redirection of TH17 cells with a CAR encoding the ICOS intracellular domain is a promising approach to augment the function and persistence of CAR T cells in hematologic malignancies.

↓ View online

Share this

How can we help?

Once you hit send…

We’ll match your inquiry to the person who can best help you.

Expect a response within 48 hours.

Career call to action image

Make your own mark.

Search jobs

Our work

Case studies

Publications

Timeline of innovation

Areas of expertise

Institute

Leadership

Press room

Media inquiries

Compliance

Careers

Job listings

Contact

SRI Ventures

Our locations

Headquarters

333 Ravenswood Ave
Menlo Park, CA 94025 USA

+1 (650) 859-2000

Subscribe to our newsletter


日本支社
SRI International
  • Contact us
  • Privacy Policy
  • Cookies
  • DMCA
  • Copyright © 2022 SRI International