<b>Methods:</b> We developed a dual-labeled probe based on A2 cys-diabody (A2cDb) targeting the cell-surface prostate stem cell antigen (PSCA), which is expressed in most pancreatic cancers.
These findings support the benefit of combining the 4/7 ICR with CAR-PSCA to treat pancreatic cancer, a PSCA-expressing tumor characterized by a dense immunosuppressive environment rich in IL-4.
While our results provide evidence to support PSCA as a target antigen for CAR-based immunotherapy of pancreatic cancer, the expression of PSCA on selected normal tissues could be a source of limiting toxicity.
Further validation showed that overexpression of PSCA was significantly associated with lymph node metastasis, and overexpression of HMGA2 was significantly associated with invasive depth of pancreatic cancer.
A monoclonal antibody against prostate stem cell antigen (PSCA) has emerged as a novel cancer therapy currently being tested in clinical trials for prostate and pancreatic cancers, but this treatment is likely to be efficient only in patients with PSCA-expressing tumors.
RNA from pancreatic and nonpancreatic cancer cell lines as well as tissue and blood from pancreatic cancer and control patients was reverse-transcribed and PSCA quantified by qPCR.
PSCA expression was present in the blood of 22 out of 47 (46.8%) patients with malignant tumors and particularly in 7 out of 11 (63.6%) patients with pancreatic cancer.
We then analyzed these 19 genes for their methylation pattern in pancreatic cancers and found that all 7 of the genes (claudin4, lipocalin2, 14-3-3sigma, trefoil factor2, S100A4, mesothelin, and prostate stem cell antigen) that were overexpressed in the neoplastic cells of pancreatic cancers and not expressed in normal pancreatic duct displayed a high prevalence of hypomethylation in pancreatic cancer cell lines and primary pancreatic carcinomas.