Radioimmunodetection of neuroblastoma: Expression of target antigen GD2 is changed by retinoic acid

Objectives There is increasing interest in the use of anti-GD2 radioimmunoimaging in the detection and therapy monitoring of neuroblastoma (NB) and in the use of GD2 for targeted treatment. Differentiating chemotherapeutics such as retinoic acid (RA) might change the cellular expression of proteins and other molecules, such as GD2. The objective of this study was to test the hypothesis that: Retinoic acid therapy of neuroblastoma cells modulates cell membrane GD2 expression.

Methods Human NB cell lines were grown for 8 d in medium containing RA at physiologically-relevant concentrations (0.01 to 10 µM, n=4). Cells were then incubated with the Cu-64-labeled anti-GD2 antibody ch14.18 for 1 h, washed to remove unbound antibody, and the Cu-64 bound to the cells was measured.

Results In all cases RA treatment changed the amount of anti-GD2 antibody binding to the cells (see table). The general pattern was a dose-response, with 10 µM RA eliciting the greatest change and antibody binding trending back to control levels at lower concentrations. Interestingly, the change varied in direction, with RA therapy resulting in decreased binding in 3 of the cell lines and increased binding in the other 3 cell lines.

Conclusions RA therapy of NB cells changed the binding of anti-GD2 antibody, presumably through changing expression of the GD2 antigen. This observation has significant implications for the clinical use of anti-GD2 radioimmunoimaging as a biomarker for monitoring response to RA chemotherapy in NB.

Research Support Society for Pediatric Radiology Seed Grant Award (to JLJD)

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Retinoic acid therapy of neuroblastoma cells leads to modulation of anti-GD2 antibody binding