CAR-T therapy targeting chondroitin sulfate offers hope for glioblastoma patients

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An international team of researchers has identified chondroitin sulfate proteoglycan 4 (CSPG4) as a new molecular target for CAR-T therapy for glioblastoma, the most lethal brain tumor.

Glioblastoma is the most frequent and malignant type of cancer that begins in the brain. Although CAR-T therapy is under development for various cancers, their use in cancers like glioblastoma is currently limited due to the heterogenous expression of tumor-associated antigens on their cell surface.

In the present study published in Science Translational Medicine, researchers at the University of North Carolina at Chapel Hill in collaboration with the Fondazione Istituto di Ricerca e Cura a Carattere Scientifico in Milan, Italy have identified CSPG4 as a potential target for CAR-T therapy.

The team led by Prof. Gianpietro Dotti found that CSPG4 was present in 67% of glioblastoma specimens with limited heterogeneity. CSPG4 was also expressed on primary-glioblastoma derived cells, grown in vitro as neurospheres; these cells mimic the histopathology and molecular characteristics of primary glioblastoma. Most importantly, CAR-T cells designed for targeting CSPG4 controlled tumor growth in these cell models and mouse models of glioblastoma.

These findings indicate CAR-T therapy against CSPG4 as a therapeutic approach to treat glioblastoma. The study could also be extended to other solid tumors that express CSPG4, thus offering the possibility to target a broad spectrum of solid tumors for which no curative treatment is currently available.

Source: Pellegatta S et al., Constitutive and TNFα-inducible expression of chondroitin sulfate proteoglycan 4 in glioblastomaand neurospheres: Implications for CAR-T cell therapy. Science Translational Medicine, February 2018. Reference