PubMed · 7016713
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P Isaacson. 1981. Immunoblastic sarcoma after thymus graft.. https://doi.org/10.1111/j.1365-2559.1981.tb01795.x
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Melanoma-associated retinopathy (MAR) is a rare paraneoplastic syndrome in patients with melanoma. Since the onset of MAR symptoms is often associated with tumor progression or recrudescence of metastases, MAR-related symptoms are prognostic relevant. The pathomechanism underlying MAR is supposed to result from antibody production against yet unknown melanoma-associated antigens that are also expressed in retinal tissue, leading to the destruction of retinal cells and resulting in defective signal transduction. Only a 35 kDa protein in Müller glial cells, a 22 kDa neuronal antigen and retinal transducin have been identified as MAR-associated antigens to date. To identify additional antigens potentially involved in the pathogenesis of MAR, we screened a retina cDNA phage library for reactivity with antibodies in the sera from 9 patients with MAR or subclinical MAR using the serological analysis of recombinantly expressed clones (SEREX) approach. Six sera from melanoma patients without evidence of MAR and 10 sera from healthy donors served as controls. Mitofilin and titin were identified as antigens against which antibodies were found exclusively in sera of MAR patients, but not in the sera of MM patients without MAR or healthy donors. This is the first study to demonstrate that titin is highly expressed from retinal tissue and melanoma. The fact that none of the MAR-associated antigens detected to date by their capacity to elicit a humoral immune response is located on the cell surface questions a major pathogenetic role of the respective antibodies and suggests that cellular, rather than humoral mechanisms are operative in the primary immune attack against the retina in MAR.
Tumor associated glycoprotein-72 (TAG-72), a pancarcinoma antigen, was initially identified in cancer tissues by its immunoreactivity to a monoclonal antibody B72.3. In this study, we have analyzed the expression and localization profiles of TAG-72 in ovarian cancer tissue samples of different stages and histological subtypes by immunohistochemistry using a second generation high affinity monoclonal antibody CC49. We have also studied the expression of TAG-72 in ovarian cancer cell lines by confocal microscopy and immunoblot analyses. A correlation between TAG-72 expression and localization with patients' prognosis was also analyzed using Kaplan-Meier analysis. Eighty eight percent of the ovarian cancer tissue samples (n=43) showed immunoreactivity with CC49 antibody. The expression of TAG-72 in advanced stage cancer tissues (mean composite score=3.7) was significantly higher (p=0.035) compared to the early stage tumors (mean composite score=2.3). However, no significant correlation of TAG-72 was observed with histological tumor types. A marginal correlation of TAG-72 staining with patients' survival was observed. Interestingly, the membrane localization of TAG-72 in tumors was significantly (p=0.0082) associated to the poor clinical outcome, while cytoplasmic staining was correlated significantly to a better prognosis (p=0.0051). Immunoblot analysis demonstrated the expression of TAG-72 in three ovarian cancer cell lines (OVCAR3, SB247 and COV362.4). In conclusion, the tumor-specific expression of TAG-72 and its association with disease stage indicate its potential as a marker for effective disease management and targeted cancer therapy.
BACKGROUND & OBJECTIVE: In malignant transformation, mutant gene products and dysregulated proteins can become tumor antigens and activate immunoreactions. Therefore, auto-antibodies exist in sera of cancer patients. Serologic analysis of recombinant cDNA expression libraries (SEREX) using autologous and allogenic patient sera provides a powerful approach to identify tumor antigens. This study was to identify esophageal cancer antigens with SEREX for serologic diagnosis, gene therapy, and immune therapy. METHODS: Expression library of cDNA from esophageal squamous cell carcinoma was constructed. SEREX screened out 21 positive clones from the 1.6x10(6) clones in the established library. The 21 positive clones were subcloned to monoclonality and submitted to in vivo excision of pBluescript phagemids. The nucleotide sequences of cDNA inserts were analyzed with DNASIS and BLAST software on EMBL and GenBank. According to the bioinformatics analyses, serologic immunoreactions of 4 colons in 10 samples of esophageal cancer serum and 10 samples of normal control serum were further detected by SADA. RESULTS: Of the 21 positive clones, 4 had no homology to any known genes, 17 were known fragments which were defined as antigens of esophageal cancer for the first time. The serologic immunoreaction rates of 4 selected antigens, including Ribosomal protein S4, and so on, were 40%, 60%, 70%, and 30%, respectively, in cancer sera, and 0%, 10%, 20%, and 20%, respectively, in normal sera. CONCLUSIONS: Antigens, such as Ribosomal protein S4, are frequently involved in serologic immunoreactions of esophageal cancer. The 21 antigens identified by the present study can be used as potential targets for gene therapy and serologic biomarkers of esophageal cancer.