Expression of PRAME and MAGE-A3 in Asian and European patients with non-small cell lung cancer (NSCLC), bladder cancer, or hepatocellular carcinoma (HCC).

Abstract

e13061 Background: Antigen (Ag)-specific cancer immunotherapy is based on induction of immune responses (humoral and cell-mediated) specifically targeting Ags expressed by tumor cells. This may be achieved by delivering the Ag as a recombinant protein combined with potent immunostimulants. PRAME and MAGE-A3 are tumor Ags with distinct tumor expression patterns, both under investigation as targets for immunotherapy in NSCLC and malignant melanoma. For additional clinical development of these immunotherapies in other cancer types, expression of PRAME and MAGE-A3 in these cancers must be investigated taking into account patient ethnicity and tumor characteristics. Methods: 4 retrospective studies were performed, each including all tumor stages: NSCLC pts (in Asia and Europe); bladder cancer pts in Europe; HCC pts in Asia. Formalin-fixed paraffin embedded tumor tissues were tested for PRAME and MAGE-A3 expression by quantitative RT-PCR using an expression cut-off value for positivity. Exploratory analyses of possible associations with patient and tumor characteristics were done to identify factors that may impact Ag expression. Results: The overall Ag expression rates are shown in the table below. In NSCLC, both Ags were expressed less frequently in Asian than in European patients (the histological distribution was the same). NSCLC tumors more frequently expressed PRAME than MAGE-A3 while the reverse tendency was seen for bladder tumors and HCC. In the NSCLC studies, squamous cell carcinomas expressed both Ags more frequently than adenocarcinomas. No study found any association between tumor stage and Ag expression. Some 60% of the tumors express at least one of the Ags. Conclusions: The expression rates of PRAME and MAGE-A3 are sufficiently high to consider these Ags as targets for immunotherapy against NSCLC, bladder cancer and HCC. [Table: see text]