Abstract
Expression of N-glycolyl GM3 (NeuGcGM3) ganglioside was detected in the tumor specimens of patients who were on Racotumomab anti-idiotype vaccine maintenance treatment, and prognostic significance as a biomarker was investigated. No statistically significant association was observed in the multivariate analysis between overall survival and tissue NeuGcGM3 IHC levels. Although numerically there was a difference favoring less intense IHC for better prognosis, this did not reach statistical power. However, there was a strong correlation between Racotumomab doses and overall survival (OS). Mean OS of the patient with more than 10 Racotumomab application was significantly longer than the patient who had less than 10 injections (70.7 months vs. 31.1 months, p < 0.001). We propose that, regardless of staining intensity, the presence of NeuGcGM3 in patient tissues might be an indicator of benefit in Racotumomab treatment.
Highlights
Numerous molecules have been considered as targets for cancer immunotherapy because of their levels of expression on tumor cells and their ability of immunogenicity
IHC staining was performed in 10 benign tissue specimens as controls. 14F7 monoclonal antibody was obtained from mice that were immunized with purified gangliosides and supplied by the manufacturer’s institute, Center of Molecular Immunology (CIM), Havana, Cuba
All 48 patients were on Racotumomab maintenance treatment following chemotherapy who had at least partial remission
Summary
Numerous molecules have been considered as targets for cancer immunotherapy because of their levels of expression on tumor cells and their ability of immunogenicity. A ganglioside GM3 (Neu5Gc) which presents on the outer surface of the plasma membrane of vertebrate cells attracted most attention as a tumor specific antigen, a target for cancer immunotherapy. The aberrant expression of the ganglioside NeuGcGM3 in certain human tumors, like lung cancer, breast cancer, neuroblastoma (Scursoni et al (Clin Dev Immunol, 2011)), pancreatic cancer, and gastrointestinal tumors, made this molecule an attractive target for immunotherapy. Ere are numerous hypotheses explaining the existence of NeuGcGM3 in human malignancies, from changing dietary habits to the modified metabolism of malignant cells as a result of genetic mutations and due to the hypoxic conditions of the tumor [7]. The aberrant expression of the ganglioside NeuGcGM3 in certain human tumors, like lung cancer, breast cancer, neuroblastoma (Scursoni et al (Clin Dev Immunol, 2011)), pancreatic cancer, and gastrointestinal tumors, made this molecule an attractive target for immunotherapy. e most common sialic acids in humans are N-acetyl (NeuAc) and N-glycolyl (NeuGc) neuraminic acids(Figure 1) [1,2,3,4,5,6].
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