Diganglioside G_D2 and Antigen 8H9: Potential Targets for Antibody-Based Immunotherapy against Desmoplastic Small Round Cell Tumor and Rhabdomyosarcoma

Abstract 873 Poster Session II, Sunday, 5/2 (poster 135)

Desmoplastic small round cell tumor (DSRCT) is an unusual primitive sarcoma of children and young adults which is characterized karyotypically by the t(11;22)(p13;q12) translocation, and molecularly by the fusion of EWS and WT1 genes. Rhabdomyosarcoma (RMS) is the third most common extracranial solid tumor of childhood. Metastatic RMS and DSRCT are chemotherapy-responsive, yet patients often relapse off therapy because of residual microscopic disease at distant sites; liver, peritoneum and lung (DSRCT); lung, marrow and bones (RMS). Strategies directed at minimal residual disease may be necessary for cure. Monoclonal antibodies selective for cell surface tumor-associated antigens (e.g. G_D2) are potential candidates as recently demonstrated in advanced-stage neuroblastoma (JCO 16: 3053, 1998). Using immunohistochemistry we studied the expression of G_D2 using the antibody 3F8, and a novel antigen using the monoclonal antibody 8H9 in a panel of 22 freshly frozen DSRCT from 18 patients (pts) and 17 RMS from 17 pts. G_D2 is a disialoganglioside widely expressed among neuroectodermal tumors as well as some sarcomas. 8H9 immunoprecipitates a surface antigen of ∼115kD expressed among neuroectodermal, mesenchymal and epithelial tumors with restricted expression on normal tissues. All DSRCTs had the characteristic EWS-WT1 fusion gene. 4 of 17 RMS had alveolar morphology and 13 were embryonal RMS. 13 of 18 pts with DSRCT had tumors reactive with 3F8, and all 18 with 8H9. G_D2 expression did not correlate with tumor stage or survival. Of the 17 RMS, 8 were reactive with 3F8 (3/4 alveolar and 5/13 embryonal), and 16 with 8H9. G_D2 expression was present in only 1 of 7 nonmetastatic RMS, in contrast to 10 of 17 metastatic RMS. While 8H9 positivity was homogenous among individual cells of diverse tumor types, G_D2 expression in RMS was more heterogenous than in DSRCT or neuroblastoma. Antibody-based immunotherapy may offer new possibilities in improving the outcome in patients with these poor-risk tumors.