The promiscuous receptor.

OBJECTIVE: To determine the effectiveness of vitamin D therapy in patients with asymptomatic, prostate-specific antigen (PSA)-progression of prostate cancer. PATIENTS AND METHODS: Twenty-six patients with locally advanced or metastatic prostate cancer were treated with vitamin D. Vitamin D therapy was discontinued on disease progression as assessed by symptoms or serum PSA increase. The response to therapy was judged from changes in PSA level from the pretreatment baseline to 3 months after starting vitamin D therapy. RESULTS: Of the 26 patients, five (20%) responded to vitamin D; the mean (range) reduction in PSA level was 45.3 (15.9-95.1)%, and mean duration of response was 4-5 months. Patients in whom the PSA level was stabilized, but not reduced, after vitamin D treatment had a duration of response of up to 36 months. Treatment was well tolerated and was not associated with elevation of serum calcium levels. There was no significant correlation between response to therapy and stage of disease, Gleason grade, previous treatments or PSA level at diagnosis or initiation of vitamin D therapy. CONCLUSION: Vitamin D therapy is an effective and well tolerated treatment for patients with asymptomatic progressive prostate cancer, and is a useful addition to the therapeutic options.

Enhanced immune recognition of cryptic glycan markers in human tumors.

Abnormal glycosylation is one of the hallmarks of the cancer cell and is associated with tumor invasion and metastasis. The development of tumor-associated carbohydrate antigen (TACA) vaccines has been problematic due to poor immunogenicity. However, when appropriate targets can be identified, passive immunization with monoclonal antibodies (mAbs) directed against TACAs has been shown to have antitumor activity. Fas ligand (FasL) is a transmembrane protein that induces apoptosis in cells expressing its receptor, Fas. When grafted into mice, FasL-expressing tumor cells break immunologic tolerance to self-antigens and induce antibody-mediated tumor immunity. Here, five IgM mAbs were produced from mice vaccinated with FasL-expressing B16F10 mouse melanoma cells. They recognize various syngeneic and allogeneic murine tumor cell lines. One mAb, TM10, recognizes a range of human tumor cell lines, including melanoma, prostate, and ovarian cancer. It does not bind to untransformed cells. The epitopes recognized by all the mAbs were carbohydrates expressed on proteins. Using carbohydrate microarrays, the antigenic targets of TM10 were found to be high-mannose core structures of N-linked glycans. In normal cells, high-mannose clusters are hidden by extensive saccharide branching but they become exposed in cancer cells as a result of abnormal glycosylation pathways. Vaccination with FasL-expressing tumors therefore enables the immune system to break tolerance to self-antigens, allowing identification of novel TACAs that can form the basis of future humoral anticancer therapy.