GD2-targeting therapy: a comparative analysis of approaches and promising directions

Front Immunol. 2024 Mar 15:15:1371345. doi: 10.3389/fimmu.2024.1371345. eCollection 2024.

Abstract

Disialoganglioside GD2 is a promising target for immunotherapy with expression primarily restricted to neuroectodermal and epithelial tumor cells. Although its role in the maintenance and repair of neural tissue is well-established, its functions during normal organism development remain understudied. Meanwhile, studies have shown that GD2 plays an important role in tumorigenesis. Its functions include proliferation, invasion, motility, and metastasis, and its high expression and ability to transform the tumor microenvironment may be associated with a malignant phenotype. Structurally, GD2 is a glycosphingolipid that is stably expressed on the surface of tumor cells, making it a suitable candidate for targeting by antibodies or chimeric antigen receptors. Based on mouse monoclonal antibodies, chimeric and humanized antibodies and their combinations with cytokines, toxins, drugs, radionuclides, nanoparticles as well as chimeric antigen receptor have been developed. Furthermore, vaccines and photoimmunotherapy are being used to treat GD2-positive tumors, and GD2 aptamers can be used for targeting. In the field of cell therapy, allogeneic immunocompetent cells are also being utilized to enhance GD2 therapy. Efforts are currently being made to optimize the chimeric antigen receptor by modifying its design or by transducing not only αβ T cells, but also γδ T cells, NK cells, NKT cells, and macrophages. In addition, immunotherapy can combine both diagnostic and therapeutic methods, allowing for early detection of disease and minimal residual disease. This review discusses each immunotherapy method and strategy, its advantages and disadvantages, and highlights future directions for GD2 therapy.

Keywords: CAR cells; cancer immunotherapy; cell therapy; clinical trials; disialoganglioside GD2; monoclonal antibody; neuroblastoma; vaccine.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Immunotherapy / methods
  • Killer Cells, Natural / metabolism
  • Mice
  • Natural Killer T-Cells*
  • Neuroblastoma* / pathology
  • Receptors, Chimeric Antigen* / genetics
  • Receptors, Chimeric Antigen* / therapeutic use
  • Tumor Microenvironment

Substances

  • Receptors, Chimeric Antigen

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was carried out with the support of the Russian Science Foundation, project number 21-65-00004 (https://rscf.ru/project/21-65-00004/, accessed on 20 April 2021).