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Monitoring response to treatment in melanoma patients: Potential of a serum glycomic marker
Author(s) -
Selvan Senthamil R.,
Dillman Robert O.,
Fowler Abner W.,
Carbonell Denysha J.,
Ravindranath Mepur H.
Publication year - 2007
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23155
Subject(s) - medicine , antibody , immunotherapy , immunology , melanoma , biomarker , gastroenterology , ganglioside , immune system , biology , cancer research , biochemistry
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, IFNγ‐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. © 2007 Wiley‐Liss, Inc.