Monitoring response to treatment in melanoma patients: potential of a serum glycomic marker.
A mechanistic marker correlating with tumor progression and clinical response is useful for assessing therapeutic response and determining the course of therapy. Since serum-total-ganglioside (sTG) and antiganglioside-IgM antibody levels reflected tumor progression, the feasibility of utilizing sTG for assessing the response to immunotherapy of metastatic-melanoma was tested. Patients (n = 34) were immunized with dendritic cells cocultured with irradiated, IFN gamma-treated autologous tumor cells admixed with GM-CSF. Levels of sTG and antiganglioside-IgM antibody titers were measured in sera of vaccine recipients at 0, 4 and 24 weeks of treatment. Based on sTG-level, whether lower (L) or higher (H) than the mean + 1 SD of normal and healthy volunteers on weeks 0, 4 and 24, patients were categorized into cohorts-I (LLL, n = 16), II (HHL/HLL, n = 4), III (LLH/LHH/LHL, n = 7) and IV (HHH/HLH, n = 7). The cohorts were regrouped as sTG- downregulators (sTG-DR; n = 20) and upregulators (sTG-UR; n = 14). These two cohorts differed significantly in their overall (p < 0.012) and progression-free (p = 0.0001) survival post-treatment. 43% sTG-UR died within 39 months, with a median survival of 39 months, whereas 61% of the sTG-DR survived for 48 months. Both endogenous and vaccine-induced antiganglioside-IgM antibodies appeared to regulate sTG levels. Nonresponders had increased sTG with no or low IgM antibody response. The sTG level is regulated within 24 weeks post-treatment and therefore, may serve as an ideal biomarker for assessing therapeutic responses in patients. Clinical correlations of sTG indicate that sTG-downregulating therapy may be an effective treatment strategy for melanoma.
Selvan
Senthamil R
SR
Cell Biology Laboratory, Hoag Cancer Center, Newport Beach, CA 92663, USA. senthamil.selvan@hoaghospital.org
Dillman
Robert O
RO
Fowler
Abner W
AW
Carbonell
Denysha J
DJ
Ravindranath
Mepur H
MH
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D005732:Gangliosides / Q000097:blood*; D006801:Humans; D007167:Immunotherapy; D008297:Male; D008545:Melanoma / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods*; D009362:Neoplasm Metastasis
D014408:Biomarkers, Tumor; D005732:Gangliosides