title: Chondroitin sulfate proteoglycan 4 as a target for chimeric antigen receptor-based T-cell immunotherapy of solid tumors.
abstract: BACKGROUND
  Proteoglycans are critical molecules involved in multiple physiological cell functions, but also key players in cancer development and progression. In particular, chondroitin sulfate proteoglycan 4 (CSPG4) is recognized as an attractive target for antibody-based approaches because of its high expression on cancer cells in several types of human malignancies and its restricted distribution in normal tissues.
  
  
  METHODS
  Adoptive transfer of genetically modified T cells is emerging as a powerful therapeutic approach in cancer patients. In this regard, the selection of the appropriate antigen to be targeted in solid tumors becomes a critical aspect in promoting potent antitumor effects while preventing toxicities. This review summarizes the authors' current knowledge on the expression and function of CSPG4 in normal tissues and malignant tumors, with a particular focus on the potential use of CSPG4 as a target for antigen-specificity redirected T cells.
  
  
  CONCLUSIONS
  T cells expressing a CSPG4-specific chimeric antigen receptor (CAR) offer the possibility to target a broad spectrum of solid tumors for which no curative treatment is currently available. In addition, since CSPG4 is also selectively up-regulated on tumor-associated pericytes, targeting this antigen may also contribute to tumor regression via inhibition of neoangiogenesis. Preclinical experiments to date justify the clinical translation of CSPG4-specific CAR-T cells.
authors.affiliation: a 1 Massachusetts General Hospital, Harvard Medical School, Department of Surgery , 55 Fruit Street, Boston, MA 02114, USA Sferrone@MGH.Harvard.edu.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: b 2 National Cancer Institute, Experimental Transplantation and Immunology Branch , Bethesda, MD 20892, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Geldres
authors.affiliation: a 1 Massachusetts General Hospital, Harvard Medical School, Department of Surgery , 55 Fruit Street, Boston, MA 02114, USA Sferrone@MGH.Harvard.edu.
authors.forename: Soldano
authors.initials: S
authors.lastname: Ferrone
authors.affiliation: c 3 University of North Carolina, Lineberger Comprehensive Cancer Center , Chapel Hill, NC, USA gdotti@med.unc.edu.|d 4 University of North Carolina, Department of Microbiology and Immunology Chapel Hill, NC, USA.
authors.forename: Gianpietro
authors.initials: G
authors.lastname: Dotti
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011509:Proteoglycans / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D011509:Proteoglycans; D011948:Receptors, Antigen, T-Cell; D000099216:Chondroitin Sulfate Proteoglycan 4
keywords: CSPG4; T-cell therapies; chimeric antigen receptor; solid tumors