Antibody response to murine anti-GD2 monoclonal antibodies: correlation with patient survival.
Clinical strategies which modulate the human anti-mouse antibody response (HAMA) in patients may have a profound influence on the idiotype network inducible by murine monoclonal antibodies (MoAb). Prior to myeloablative chemotherapy (ABMT), 9 patients with Stage IV neuroblastoma were imaged with 131I-3F8, a MoAb specific for the ganglioside GD2. Their serum HAMA, anti-idiotypic, anti-GD2, and anti-anti-idiotypic antibodies were assayed by enzyme-linked immunosorbent assay prior to, and at 3 and 6 months postimaging. HAMA and anti-idiotypic levels remained low, in contrast to the high levels in 10 patients imaged with 131I-3F8 without ABMT. Five of the 9 patients are long-term survivors; all had elevated anti-GD2 and anti-anti-idiotypic levels, significantly higher than those who died of disease. Although 131I-3F8 imaging prior to ABMT detected abnormal sites in 4 of 9 patients, 3 of the 4 patients have continued in remission for 24-63 months after ABMT, and all 3 mounted anti-GD2 and anti-anti-idiotypic antibody responses. We conclude that myeloablative therapy strongly suppressed the HAMA/anti-idiotypic response to murine MoAb and that the prognostic significance of host immune response to ganglioside GD2 MoAb deserves further investigation.
Cheung
N K
NK
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Cheung
I Y
IY
Canete
A
A
Yeh
S J
SJ
Kushner
B
B
Bonilla
M A
MA
Heller
G
G
Larson
S M
SM
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D000917:Antibody Formation; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D002330:Carmustine / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D004797:Enzyme-Linked Immunosorbent Assay; D005047:Etoposide / Q000008:administration & dosage; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D008558:Melphalan / Q000008:administration & dosage; D051379:Mice / Q000276:immunology; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011379:Prognosis; D011879:Radiotherapy Dosage; D016019:Survival Analysis; D015996:Survival Rate; D013852:Thiotepa / Q000008:administration & dosage
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D005732:Gangliosides; C019403:ganglioside, GD2; D005047:Etoposide; D013852:Thiotepa; D002945:Cisplatin; D008558:Melphalan; D002330:Carmustine