Monitoring response to treatment in melanoma patients: Potential of a serum glycomic marker

Abstract

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 5 34) were immunized with dendritic cells cocultured with irradiated, IFNc-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 1 SD of normal and healthy volunteers on weeks 0, 4 and 24, patients were categorized into cohorts-I (LLL, n 5 16), II (HHL/HLL, n 5 4), III (LLH/LHH/LHL, n 5 7) and IV (HHH/HLH, n 5 7). The cohorts were regrouped as sTG-downregulators (sTG-DR; n 5 20) and upregulators (sTG-UR; n 5 14). These two cohorts differed significantly in their overall (p < 0.012) and progression-free (p 5 0.0001) survival posttreatment. 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 antigangliosideIgM 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.

Augmentation of anti-HLA-E antibodies with concomitant HLA-Ia reactivity in IFNγ-treated autologous melanoma cell vaccine recipients*

“…This study utilized archived sera of patients that participated in the clinical trial NCI-V01-1646, at the Hoag Cancer Center. The sera and tumor cells were obtained after Institutional Review Board approval and patient consent (Selvan et al, 2008). The preparation of autologus vaccine was described in detail elsewhere (Selvan et al, 2008).…”

“…Towards this objective, the present investigation assessed whether anti-HLA-E antibodies can be augmented in melanoma patients by immunizing patients with autologous melanoma cells grown in IFNγ (that enhances the expression of HLA-E) (Derre et al, 2006). The autologous melanoma vaccine recipient cohort was considered ideal for this study since these patients received autologous tumor cells treated with IFNγ (Selvan et al, 2008(Selvan et al, , 2010. To find out if HLA-E on the autologous melanoma cells elicit antibodies in patients, sera of Stage III/Stage IV patients obtained at Weeks 0, 4, and 24 after vaccinating with the autologous tumor cells (admixed with dendritic cells [DC]) were analyzed for anti-HLA-E Abs.…”

Characterization of Interferon-γ–Treated Melanoma Tumor Cells for Use in Dendritic Cell-Based Immunotherapy

“…19 The IFN-c-treated and irradiated tumor cells were recovered from cryopreservation, washed 3 · with PBS, and then added to the in vitro cultivated DCs and incubated for *24 hours. The antigen-loaded DCs were harvested by gentle scraping with a rubber policeman and cryopreserved at equal amounts in 9-11 aliquots.…”

Advent of a Link between Ayurveda and Modern Health Science: The Proceedings of the First International Congress on Ayurveda, “Ayurveda: The Meaning of Life—Awareness, Environment, and Health” March 21‐22, 2009, Milan, Italy

“…Dr. Selvan illustrated how the cross-talk between the immune system and cancer ultimately shapes cancer elimination, evasion, or even progression. He referred to his cutting-edge combinatorial personalized cancer treatment clinical trial with tumor-reduction surgery followed by vaccination with tumor-associated antigens that is aimed at boosting the immune system to ultimately eliminate tumors [14, 15]. He evaluated that various immunotherapeutic clinical trials used so far have only yielded benefit to a subset of patients [16].…”