IGF1R- and ROR1-Specific CAR T Cells as a Potential Therapy for High Risk Sarcomas. Academic Article uri icon

Overview

abstract

  • Patients with metastatic or recurrent and refractory sarcomas have a dismal prognosis. Therefore, new targeted therapies are urgently needed. This study was designed to evaluate chimeric antigen receptor (CAR) T cells targeting the type I insulin-like growth factor receptor (IGF1R) or tyrosine kinase-like orphan receptor 1 (ROR1) molecules for their therapeutic potential against sarcomas. Here, we report that IGF1R (15/15) and ROR1 (11/15) were highly expressed in sarcoma cell lines including Ewing sarcoma, osteosarcoma, alveolar or embryonal rhabdomyosarcoma, and fibrosarcoma. IGF1R and ROR1 CAR T cells derived from eight healthy donors using the Sleeping Beauty (SB) transposon system were cytotoxic against sarcoma cells and produced high levels of IFN-γ, TNF-α and IL-13 in an antigen-specific manner. IGF1R and ROR1 CAR T cells generated from three sarcoma patients released significant amounts of IFN-γ in response to sarcoma stimulation. The adoptive transfer of IGF1R and ROR1 CAR T cells derived from a sarcoma patient significantly reduced tumor growth in pre-established, systemically disseminated and localized osteosarcoma xenograft models in NSG mice. Infusion of IGF1R and ROR1 CAR T cells also prolonged animal survival in a localized sarcoma model using NOD/scid mice. Our data indicate that both IGF1R and ROR1 can be effectively targeted by SB modified CAR T cells and that such CAR T cells may be useful in the treatment of high risk sarcoma patients.

publication date

  • July 14, 2015

Research

keywords

  • Bone Neoplasms
  • Receptor Tyrosine Kinase-like Orphan Receptors
  • Receptors, Antigen, T-Cell
  • Receptors, Somatomedin
  • Sarcoma
  • T-Lymphocytes

Identity

PubMed Central ID

  • PMC4501840

Scopus Document Identifier

  • 84940676094

Digital Object Identifier (DOI)

  • 10.1158/2326-6066.CIR-14-0163

PubMed ID

  • 26173023

Additional Document Info

volume

  • 10

issue

  • 7