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posted on 2023-04-03, 23:02 authored by Darshil T. Jhaveri, Min-Sik Kim, Elizabeth D. Thompson, Lanqing Huang, Rajni Sharma, Alison P. Klein, Lei Zheng, Dung T. Le, Daniel A. Laheru, Akhilesh Pandey, Elizabeth M. Jaffee, Robert A. Anders Additional immunohistochemical validation showing PSMC5, MYPT1 and TFRC expression in an independent set of pancreatic cancers.
Funding
NIH
Viragh Foundation and the Skip Viragh Pancreatic Cancer Center at Johns Hopkins
The National Pancreas Foundation
Lefkofsky Family Foundation
NCI
Lustgarten Foundation
Sol Goldman Pancreatic Cancer Center
NIH, NCI and National Heart, Lung and Blood Institute, and the Sol Goldman Pancreatic Cancer Research Center
History
ARTICLE ABSTRACT
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.
