T lymphocytes redirected against the chondroitin sulfate proteoglycan-4 control the growth of multiple solid tumors both in vitro and in vivo

  • Geldres C
  • Savoldo B
  • Hoyos V
 et al. 
  • 47

    Readers

    Mendeley users who have this article in their library.
  • 20

    Citations

    Citations of this article.

Abstract

PURPOSE: Because of its high expression on various types of tumors and its restricted distribution in normal tissues, chondroitin sulfate proteoglycan-4 (CSPG4) represents an attractive target for the antibody-based therapy of several solid tumors. We tested whether T cells transduced with a CSPG4-specific chimeric antigen receptor (CAR) inhibited the growth of CSPG4-expressing tumor cells both in vitro and in vivo.

EXPERIMENTAL DESIGN: We first independently validated by immunohistochemistry (IHC) the expression of CSPG4 in an extensive panel of tumor arrays and normal tissues as well as queried public gene expression profiling datasets of human tumors. We constructed a second-generation CSPG4-specific CAR also encoding the CD28 costimulatory endodomain (CAR.CSPG4). We then evaluated human T lymphocytes expressing this CAR for their ex vivo and in vivo antitumor activity against a broad panel of solid tumors.

RESULTS: IHC showed that CSPG4 is highly expressed in melanoma, breast cancer, head and neck squamous cell carcinoma (HNSCC), and mesothelioma. In addition, in silico analysis of microarray expression data identified other important potential tumors expressing this target, including glioblastoma, clear cell renal carcinoma, and sarcomas. T lymphocytes genetically modified with a CSPG4-CAR controlled tumor growth in vitro and in vivo in NSG mice engrafted with human melanoma, HNSCC, and breast carcinoma cell lines.

CONCLUSIONS: CAR.CSPG4-redirected T cells should provide an effective treatment modality for a variety of solid tumors.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Get full text

Authors

  • Claudia Geldres

  • Barbara Savoldo

  • Valentina Hoyos

  • Ignazio Caruana

  • Ming Zhang

  • Eric Yvon

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free