Chondroitin Sulfate Proteoglycan 4 and Its Potential As an Antibody Immunotherapy Target across Different Tumor Types

Our plain-English summary of Chondroitin Sulfate Proteoglycan 4 and Its Potential As an Antibody Immunotherapy Target across Different Tumor Types, by K.M. Ilieva, A. Cheung, S. Mele, et al (Frontiers in Immunology, 2017).

The study

• Authors: K.M. Ilieva, A. Cheung, S. Mele, G. Chiaruttini, S. Crescioli, M. Griffin, M. Nakamura, J.F. Spicer, S. Tsoka, K.E. Lacy, A.N.J. Tutt, S.N. Karagiannis
• Journal: Frontiers in Immunology
• Published: 2017;8:1911
• Type of article: Review
• Cited by: 112 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Overexpression of the chondroitin sulfate proteoglycan 4 (CSPG4) has been associated with the pathology of multiple types of such as melanoma, breast cancer, squamous cell carcinoma, mesothelioma, neuroblastoma, adult and pediatric sarcomas, and some hematological cancers. CSPG4 has been reported to exhibit a role in the growth and survival as well as in the spreading and metastasis of tumor cells. CSPG4 is overexpressed in several malignant diseases, while it is thought to have restricted and low expression in normal tissues. Thus, CSPG4 has become the target of numerous anticancer treatment approaches, including monoclonal antibody-based therapies. This study reviews key potential anti-CSPG4 antibody and immune-based therapies and examines their direct antiproliferative/metastatic and immune activating mechanisms of action.

In plain English

This article was a review, not a new study. The authors summarized published research on CSPG4 (chondroitin sulfate proteoglycan 4), a protein on the surface of cells, and on antibody and immune-cell treatments aimed at it. They described reports that CSPG4 is found at high levels in several cancers, including melanoma, triple-negative breast cancer, glioma, head and neck cancer, sarcomas, some leukemias and malignant mesothelioma, while normal tissues are thought to have low, restricted levels. The article did not study asbestos or any asbestos exposure. For mesothelioma, the review cited two earlier studies. In one, a mouse antibody called TP41.2 reduced tumor growth and prolonged survival in mice carrying mesothelioma. In the other, CSPG4-targeted engineered T cells killed mesothelioma and other cancer cell lines in the laboratory. Most of the evidence reviewed came from cell and animal experiments. The clinical results cited came from small early trials in melanoma. The authors concluded that CSPG4 is a promising therapy target. They called for studies with human or humanized antibodies and for evaluation of side effects in normal tissues.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published laboratory, animal and early clinical studies
• Who was studied: No study population of its own. The review covered published studies on CSPG4 in several tumor types, including melanoma, breast cancer, squamous cell carcinoma, mesothelioma, neuroblastoma, sarcomas and hematological cancers.
• Exposure: No asbestos or fiber exposure was studied. The subject was CSPG4-targeting treatments: classic monoclonal antibodies, anti-idiotypic antibodies, bispecific T cell engagers, CAR T cells, radioimmunotherapy and cytolytic fusion proteins.
• Main results:
  • Mesothelioma, as reported from an earlier study: the mouse antibody TP41.2 reduced mesothelioma cell proliferation, adhesion, motility, migration and invasion in the laboratory. It also reduced tumor growth and prolonged survival in mesothelioma-bearing SCID mice.
  • Earlier study: anti-CSPG4 CAR T cells killed several solid tumor cell lines in the laboratory, including mesothelioma.
  • Earlier report: CSPG4 RNA was found in many normal tissues, but at levels 6.6 times lower than in tumors.
  • Earlier reports: CSPG4 is expressed in over 70% of melanomas.
  • Earlier phase I trial: radioimmunotherapy with (213)Bi-cDTPA-9.2.27 in advanced melanoma showed no toxicities and a 10% objective partial response rate.
  • Earlier phase I trial: the anti-idiotypic antibody MF11-30 was followed by complete remission in one advanced melanoma patient and minor survival benefits in three others.
  • Earlier immune monitoring study: T cell reactivity to CSPG4 was seen in 11 of 42 melanoma patients, compared with 11 of 13 healthy volunteers.
• The authors' conclusion: The authors concluded that CSPG4's overexpression in tumors, its low and restricted presence in normal tissues, and its reported roles in cancer growth identify it as a promising target for therapies, including monoclonal antibodies. They said further studies with humanized or human antibodies are needed.
• Limitations the authors state:
  • Most of the published antibody studies used antibodies with mouse Fc regions.
  • The role of CSPG4 in the immunology of cancer is still largely unexplored.
  • CSPG4 is present at low levels in some normal tissues, so possible toxic effects on normal tissue need evaluation.
  • It is not yet established whether CAR T cell responses seen in blood cancers can be reproduced in solid tumors.

Topics

Medical terms in this study, explained in our Lexicon: Immunotherapy, Pathology, Squamous Cell Carcinoma, Mesothelioma, Sarcoma, Metastasis, Monoclonal Antibody.

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