Abstract 4984: Chemotherapy induces a coordinate autoantibody and T-cell response against tumor-associated antigens in pancreatic cancer patients

Abstract

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most difficult cancer to treat, both for lack of effective screening method and for resistance phenomenon. At present surgical resection is the only potentially curative option, but the absence of early symptoms or clinical-pathological markers results in diagnosis at a late, inoperable stage in mostly of cases. Once diagnosed, a number of chemotherapy (CTX), radiation and combination therapy regimens are usually used to treat patients, but responses remain poor. However, chemotherapy is able to enhance tumor immunogenicity. Thus more immunogenic tumor associated antigens (TAA) can be induced by CTX and targeted by passive or active immunotherapy. We have previously identified a number of TAAs that are recognized by autoantibodies in PDAC patients. One of these, alpha-enolase (ENO1), was found to have good antigenic capability and immunization with DNA coding for ENO1 effectively enhanced the survival of genetically engineered mice that develop spontaneously PDAC. To discover TAAs that might be selected for immunotherapy, we have analyzed autoantibody response in 19 PDAC patients’ sera before and after CTX. The reactivity of PDAC patients’ sera obtained was analyzed on 2-dimensional gel electrophoresis proteome map of CF-PAC1 pancreatic cancer cell line and TAAs recognized by IgG autoantibodies were identified by mass spectrometry. The antibody response against 25 proteins was induced or up-regulated after CTX. Among CTX-induced TAA identified, only four, namely ENO1, FUBP1, CK8 and G6PDH were found able to ex novo induce or up-regulate IgG response in more than seven patients were selected and their ability to activate proliferation of autologous PBMC was evaluated following in vitro stimulation with the corresponding recombinant proteins. Notably, mostly of autologous T cells obtained after CXT displayed an increased proliferation in response to at least one or more of the four selected TAA after in vitro stimulation compared to autologous T cells obtained before CTX. Experiments are in progress to validate these CTX- induced TAA in a mouse model of PDAC and to evaluate the therapeutic value of the combination of CTX with the immunotherapy against these TAAs. Citation Format: Francesco Novelli, Giorgia Mandili, Emanuela Mazza, Sonia Bulfamante Bulfamante, Daniele Giordano, Laura Follia, Paola Cappello. Chemotherapy induces a coordinate autoantibody and T-cell response against tumor-associated antigens in pancreatic cancer patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4984.