Disialoganglioside GD2 and a novel tumor antigen: potential targets for immunotherapy of desmoplastic small round cell tumor.
BACKGROUND
Desmoplastic small round cell tumor (DSRCT) is an aggressive and often misdiagnosed neoplasm of children and young adults. It is chemotherapy-sensitive, yet patients often relapse off therapy because of residual microscopic disease at distant sites: peritoneum, liver, lymph node, and lung. Strategies directed at minimal residual disease (MRD) may be necessary for cure. Monoclonal antibodies selective for cell surface tumor-associated antigens may have utility for diagnosis and therapy of MRD, as recently demonstrated in advanced-stage neuroblastoma (JCO 16: 3053, 1998). We examined DSRCT samples for the expression of two tumor antigens that could serve as possible targets for antibody-based immunotherapeutic approaches.


METHODS
Using immunohistochemistry, we studied the expression of two antigens: (1) G(D2) using antibody 3F8 and (2) a novel antigen using antibody 8H9 in a panel of 46 freshly frozen DSRCT. G(D2) is a disialoganglioside, which is widely expressed among neuroectodermal tumors as well as adult sarcomas. 8H9 recognizes a 58 kDa surface antigen expressed among neuroectodermal, mesenchymal, and epithelial tumors with restricted expression on normal tissues.


RESULTS
Thirty-two of 46 (70%) tumors were reactive with 3F8, and 44 of 46 (96%) with 8H9. Both G(D2) and the 58 kDa antigen were localized to tumor cell membrane and stroma. In general, immunoreactivity was stronger and more homogeneous with 8H9 than with 3F8. There was no correlation between expression of either antigen or clinical outcome.


CONCLUSIONS
G(D2) and the novel tumor antigen recognized by 8H9 are potential targets for immunodiagnosis and antibody-based therapy of DSRCT. Med Pediatr Oncol 2002;39:547-551.
Modak
Shakeel
S
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. .
Gerald
William
W
Cheung
Nai-Kong V
NK
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000276:immunology; D000954:Antigens, Surface / Q000032:analysis; D005260:Female; D005732:Gangliosides / Q000032:analysis* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007150:Immunohistochemistry; D007159:Immunologic Tests; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy
C419226:3F8 antibody; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D005732:Gangliosides; D007074:Immunoglobulin G; C019403:ganglioside, GD2