Ganglioside SSEA-4 in Ewing sarcoma marks a tumor cell population with aggressive features and is a potential cell-surface immune target

Silke Jamitzky ¹, Bianca Altvater ^1,2, Carolin Krekeler ¹

⁰Department of Pediatric Hematology and Oncology, University Children's Hospital Muenster, Albert-Schweitzer Campus 1, 38149, Muenster, Germany.

Scientific Reports +

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May 24, 2024

View abstract on PubMed

Summary

Stage-specific embryonic antigen-4 (SSEA-4), a marker of immature cells, is highly expressed in Ewing sarcoma and linked to tumor aggressiveness. Engineered T cells targeting SSEA-4 show promise for Ewing sarcoma immunotherapy.

Area Of Science

Oncology
Immunology
Developmental Biology

Background

Aberrant expression of carbohydrate markers from immature cells occurs in cancers.
Stage-specific embryonic antigen-4 (SSEA-4) is a candidate immune target in Ewing sarcoma (EwS).

Purpose Of The Study

To evaluate SSEA-4 as a therapeutic immune target in Ewing sarcoma.
To investigate the association of SSEA-4 expression with EwS tumor aggressiveness and its potential for CAR T-cell therapy.

Main Methods

Detected SSEA-4 expression in EwS cell lines and primary tumor biopsies.
Assessed the correlation between SSEA-4 expression levels and tumor cell proliferation, chemoresistance, and migration.
Utilized a murine xenograft model to study SSEA-4 expression dynamics.
Engineered SSEA-4-specific chimeric antigen receptors (CARs) on T cells for in vitro efficacy testing.

Main Results

SSEA-4 was expressed on all tested EwS cell lines and 68% of primary tumors.
High SSEA-4 expression correlated with increased tumor cell proliferation, colony formation, chemoresistance, and migration.
SSEA-4 expression levels were independent of EWSR1-FLI1 fusion transcript or epithelial/mesenchymal plasticity markers.
SSEA-4-targeted CAR T cells demonstrated specific interaction and effective lysis of EwS cells in vitro.

Conclusions

SSEA-4 is stably expressed and functionally significant in Ewing sarcoma.
SSEA-4 represents an attractive and clinically translatable therapeutic immune target for Ewing sarcoma.