CG-8123

Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States. Less than 6% of patients survive beyond the fifth year due to inadequate early diagnostics and ineffective treatment options. Our laboratory has developed an allogeneic, granulocyte-macrophage colony-stimulating factor (GM-CSF)–secreting pancreatic cancer vaccine (GVAX) that has been tested in phase II clinical trials. Here, we employed a serum antibodies–based SILAC immunoprecipitation (SASI) approach to identify proteins that elicit an antibody response after vaccination. The SASI approach uses immunoprecipitation with patient-derived antibodies that is coupled to quantitative stable isotope–labeled amino acids in cell culture (SILAC). Using mass spectrometric analysis, we identified more than 150 different proteins that induce an antibody response after vaccination. The regulatory subunit 12A of protein phosphatase 1 (MYPT1 or PPP1R12A), regulatory subunit 8 of the 26S proteasome (PSMC5), and the transferrin receptor (TFRC) were shown to be pancreatic cancer–associated antigens recognized by postvaccination antibodies in the sera of patients with favorable disease-free survival after GVAX therapy. We further interrogated these proteins in over 80 GVAX-treated patients' pancreases and uniformly found a significant increase in the expression of MYPT1, PSMC5, and TFRC in neoplastic compared with non-neoplastic pancreatic ductal epithelium. We show that the novel SASI approach can identify antibody targets specifically expressed in patients with improved disease-free survival after cancer vaccine therapy. These targets need further validation to be considered as possible pancreatic cancer biomarkers. Cancer Immunol Res; 4(3); 225–33. ©2016 AACR.

Cell Genesys (formerly Somatix Therapy Corp) is developing GVAX as a potential cancer vaccine for various tumor types. Clinical trials have commenced for melanoma, renal tumor, lung tumor, pancreatic tumor, prostate tumor and multiple myeloma [191143], [287470], [298308], [367408], [401114]; trials are planned for 2001 in leukemia (phase I) and pancreatic cancer (phase II) [366918], [388814]. A worldwide collaboration was signed with Japan Tobacco in December 1998, covering the application of GVAX in prostate cancer trials [312213]. This collaboration may be extended to lung cancer and melanoma, depending on the clinical trial results for prostate cancer [309873], [311835]. The Japanese clinical trials were put on hold on 21 September 2000 due to problems with the mass production of cells by Cell Genesys [384885]. Somatix was developing GVAX until its merger with Cell Genesys in June 1997 [248422]. In April 2001, Cell Genesys initiated the first in a series of trials of a high-potency version of GVAX prostate cancer vaccine following encouraging phase II data reported for its first-generation product. The high-potency form of GVAX is similar to the first-generation product except that it releases an increased quantity of immune system stimulant [405932].