Carbohydrate Targets for CAR T Cells in Solid Childhood Cancers

Area of Science:

• Oncology
• Immunology
• Glycobiology

Background:

• Solid tumor treatment faces challenges due to a lack of specific target antigens for Chimeric Antigen Receptor (CAR) T-cell therapy.
• Embryonal cancers, originating from specific tissues, can express membrane-bound gangliosides, such as G_D2 on neuroblastomas.
• Gangliosides play roles in cell signaling, proliferation, and adhesion, and aberrant glycosylation patterns in cancer can promote tumor growth and metastasis.

Purpose of the Study:

• To review the role and function of membrane-expressed non-protein antigens, specifically gangliosides and abnormal protein glycosylation.
• To discuss the potential of these antigens as targets for CAR T-cell therapy in pediatric solid cancers.

Main Methods:

• Literature review summarizing current knowledge on gangliosides and protein glycosylation in pediatric cancers.
• Analysis of existing and preclinical data on CAR T-cell strategies targeting these non-protein antigens.

Main Results:

• Gangliosides like G_D2 are highly expressed on neuroblastomas and are being explored for CAR T-cell therapy, with early clinical trials showing activity.
• Other carbohydrate targets, including O-acetyl-G_D2, NeuGc-GM3, G_D3, SSEA-4, and oncofetal glycosylation variants, are under preclinical investigation.
• Aberrant glycosylation patterns offer additional immune targets distinct from protein-based screening methods.

Conclusions:

• Membrane-expressed gangliosides and aberrant protein glycosylation represent attractive, tumor-specific targets for CAR T-cell therapy in pediatric solid tumors.
• Targeting these non-protein antigens holds significant promise for advancing immunotherapy in challenging pediatric cancers.
• Further research and development of CAR T-cells targeting these novel antigens are warranted.