Anti-MAGEA1 monoclonal antibody, clone TQ205

This study aimed to evaluate the diagnostic efficacy of seven autoantibodies in all lung cancer, lung adenocarcinoma, lung squamous cell carcinoma and early-stage lung cancer patients. ELISA testing of a seven autoantibody panel was performed on 386 lung cancer patients and 238 normal controls. The sensitivity and specificity of each autoantibody were analyzed using the receiver operating characteristic curve analysis. The diagnostic efficacy of a combination of these seven autoantibodies was evaluated by binary logistic regression. The results indicated that six of the seven autoantibodies (p53, SOX2, GAGE7, GBU4-5, MAGEA1 and CAGE) had high specificity and low sensitivity, while PGP9.5 had high sensitivity and low specificity. Further analysis showed that all seven autoantibodies had better diagnostic value in lung squamous cell carcinoma patients when compared to lung adenocarcinoma or all lung cancer patients. Logistic regression showed that a combination of the seven autoantibodies resulted in more reliable detection of lung cancer than any individual autoantibody in early-stage lung cancer (sensitivity/specificity: 47.8%/81.4%, areas under the curve: 0.764, 95% confidence interval: 0.718-0.811). Additionally, this panel had a better sensitivity of 56.5% for detection of lung squamous cell carcinoma than for all lung cancer (50.1%) or adenocarcinoma (51.7%) (P< 0.05). Our results indicated that the seven autoantibody panel could be used for early lung cancer detection, and it had better sensitivity in diagnosis of lung squamous cell carcinoma.

Azanucleoside DNA-hypomethylating agents have remarkable clinical activity in myelodysplastic syndromes and acute myeloid leukemia (AML), particularly at low, non-cytotoxic doses favoring hypomethylation over cytotoxicity. Cancer/testis antigens (CTAs) encoding immunogenic proteins are not expressed in almost all normal tissues and many tumor types, but are consistently derepressed by epigenetically active agents in various cancer cell lines. Since the expression of CTA genes is usually very low or absent in myeloid leukemias, we treated various AML cell lines with 5-aza-2'-deoxycytidine (DAC) and quantified mRNA expression of the CTAs NY-ESO-1, MAGEA1, MAGEA3 and MAGEB2. Consistent time-and dose-dependent reactivation of all 4 CTA genes was observed, with maximum mRNA levels 72-144 h after treatment start. As determined by RNA microarray analyses, numerous other CTA genes (all located on the X-chromosome) were also derepressed in a time-dependent fashion by DAC. NY-ESO-1 derepression was confirmed at the protein level. By Elispot and chromium release assays we showed that the de novo expressed NY-ESO-1 protein was naturally processed and presented in a time- and dose-dependent fashion up to 8 days after the start of DAC treatment, and converted the cell lines susceptible to antigen-specific recognition by CD8+ T-cell clones. In conclusion, NY-ESO-1 and numerous other CTAs localized on the X-chromosome are readily and transiently derepressed in AML cell lines treated with DAC. The susceptibility of DAC-treated AML cell lines to antigen-specific T-cell recognition has clear implications for future clinical trials combining DAC and specific immunotherapy in AML. (C) 2010 Elsevier Ltd. All rights reserved.