Identification Of Neoantigens Recognized By Autoantibodies In Chemotherapy-Treated Pancreatic Cancer Patients

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PAPancreatic ductal adenocarcinoma (PDA) 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, 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 neo-antigens can be induced by chemotherapy and targeted by passive or active immunotherapy. We have previously identified a number of Tumor Associated Antigens (TAA) that are recognized by autoantibodies in PDAC patients. One of these, alpha-enolase, was found to have good antigen capability and immunization with DNA coding for alpha-enolase effectively enhanced the survival of genetically engineered mice that develop spontaneously PDAC. To discover neo-antigens that might be selected for immunotherapy, we have analysed antibody response in PDAC patients’ sera before and after chemotherapy. The reactivity of PDAC patients’ sera obtained before and after two rounds of chemotherapy was analysed on 2-dimensional gel electrophoresis proteome map of CF-PAC pancreatic cancer cell line and the antigens recognized by autoantibodies were identified by mass spectrometry. A number of antigens, mainly metabolic enzymes, proteins involved in transcription and structural proteins, were recognized by autoantibody only after one or two rounds of chemotherapy. The identification of common and individual antigens from chemotherapy treated-patients formed the platform for ongoing immunological studies aimed to assess the ability of these neo-antigens, compared to that identified before chemotherapy treatment, to induce specific helper and cytotoxic response to PDAC. A stronger and sustained immune response correlated to survival is expected to be induced by neo-antigens. Validation of these neo-antigens will allow to develop specific immunotherapy combined with chemotherapy.Citation Format: Giorgia Mandili, Emanuela Mazza, Michela Capello, Daniele Giordano, Paola Cappello, Francesco Novelli. Identification of neoantigens recognized by autoantibodies in chemotherapy-treated pancreatic cancer patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1329. doi:10.1158/1538-7445.AM2015-1329