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Chondroitin sulfate proteoglycan 4 as a target for chimeric antigen receptor-based T-cell immunotherapy of solid
Yangyang Wang1, Claudia Geldres2, Soldano Ferrone1
1a 1 Massachusetts General Hospital, Harvard Medical School, Department of Surgery , 55 Fruit Street, Boston, MA 02114, USA Sferrone@MGH.Harvard.edu.
Introduction:
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.
Areas Covered:
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.
Expert Opinion:
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.
Insights
Chondroitin sulfate proteoglycan 4 (CSPG4) is a promising target for cancer immunotherapy. CSPG4-specific CAR-T cells show potential for treating solid tumors and inhibiting tumor growth by targeting cancer cells and tumor vasculature.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Biology
Background:
- Proteoglycans play roles in cell function and cancer progression.
- Chondroitin sulfate proteoglycan 4 (CSPG4) is highly expressed on various cancer cells.
- CSPG4 has limited expression in normal tissues, making it an attractive cancer target.
Purpose of the Study:
- To review the expression and function of CSPG4 in normal and malignant tissues.
- To evaluate CSPG4 as a target for antigen-specific redirected T cell therapy.
- To discuss the potential of CSPG4-targeting CAR-T cells for cancer treatment.
Main Methods:
- Review of current knowledge on CSPG4 expression and function.
- Focus on adoptive transfer of genetically modified T cells.
- Analysis of CSPG4's role in solid tumors and normal tissues.
Main Results:
- CSPG4 is highly expressed on multiple solid tumors.
- CSPG4 is also found on tumor-associated pericytes, affecting neoangiogenesis.
- Preclinical data support the clinical application of CSPG4-specific CAR-T cells.
Conclusions:
- CSPG4-specific CAR-T cells can target a wide range of solid tumors.
- Targeting CSPG4 may inhibit tumor growth by affecting cancer cells and tumor vasculature.
- Clinical translation of CSPG4-targeted CAR-T cell therapy is warranted.
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