Dr Jekyll Tumor Glycolipids

Many glycolipids have been extensively studied as tumor-associated antigens and potential targets of anti-cancer therapies, primarily on melanomas. The GD3 ganglio-side has a restricted distribution on normal brain cells, connective tissue, and a small population of T cells, and is considered to be only weakly immunogenic. In comparison,

GM2 is expressed in the brain and at secretory borders of all epithelial tissues and has been shown to be highly immunogenic. Fucosyl-GMl (Fuca1-2Galß1-3GalNAca1-4[NeuAca2-3]-Galß1-4Glcß1-1Cer) is only sparsely expressed in the thymus, spleen, small intestine, and islet cells of the pancreas [96], and seems to be the most immunogenic of all three. The presence of serum antibodies against ganglioside GM2 is associated with prolonged disease-free survival in melanoma patients [97]. Similarly, induction of anti-GD3 immunity through vaccination with an anti-idiotypic monoclonal antibody that mimics GD3 correlated with prolonged survival of small cell lung cancer patients [97]. Also in small cell lung cancer patients, who were previously treated with chemotherapy and radiation therapy, Fucosyl-GM1 immunity was induced by vaccination with bovine Fucosyl-GMl conjugated to the carrier protein keyhole limpet hemocyanin (KLH) and mixed with QS-21 as adjuvant. All patients showed humoral responses, IgM and IgG1 isotype, specific to Fucosyl-GMl [97] that demonstrated complement binding activity and complement dependent cytotoxicity of tumor cells in vitro. A similar vaccination study was performed to target GM2 in previously untreated melanoma patients. Immune response was seen in form of GM2-specific IgM, IgG1 and IgG3 antibodies [98, 99]. In a more recent study, synthetic fucosyl-GMl injected with QS-21 to patients with SCLC induced only Ig-specific antibodies that were unable to mediate antibody-dependent cellular cytotoxicity [100].

GM2, GD2 and GD3 have also been used as targets of passive immunotherapy. A murine IgG3 monoclonal antibody specific for GD2 was administered to patients with metastatic neuroblastoma or melanoma [101]. This antibody could activate human complement and mediate ADCC in vitro. Two patients (12%) showed complete tumor regression and four patients had a partial or mixed antitumor response. A human IgM monoclonal antibody specific for GD2 has been administered intral-esionally in patients with metastatic melanoma. Regression was seen in almost all patients, with evidence of tumor degeneration, fibrosis, free melanin, and some degree of lymphocyte or macrophage infiltration [102]. Administration of a GD3-specific murine monoclonal IgG3 antibody produced lymphocyte and mast cell infiltration, mast cell degranulation, and complement deposition in the injected lesion. In 25% of the patients major tumor regression was observed [103].

How To Prevent Skin Cancer

How To Prevent Skin Cancer

Complete Guide to Preventing Skin Cancer. We all know enough to fear the name, just as we do the words tumor and malignant. But apart from that, most of us know very little at all about cancer, especially skin cancer in itself. If I were to ask you to tell me about skin cancer right now, what would you say? Apart from the fact that its a cancer on the skin, that is.

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