Ontology highlight
ABSTRACT: Objectives
Single-agent immunotherapy is ineffective against poorly immunogenic cancers, including pancreatic ductal adenocarcinoma (PDAC). The aims of this study were to demonstrate the feasibility of production of novel autologous tumor lysate vaccines from resected PDAC tumors, and verify vaccine safety and efficacy.Methods
Fresh surgically resected tumors obtained from human patients were processed to enzymatically synthesize α-gal epitopes on the carbohydrate chains of membrane glycoproteins. Processed membranes were analyzed for the expression of α-gal epitopes and the binding of anti-Gal, and vaccine efficacy was assessed in vitro and in vivo.Results
Effective synthesis of α-gal epitopes was demonstrated after processing of PDAC tumor lysates from 10 different patients, and tumor lysates readily bound an anti-Gal monoclonal antibody. α-gal(+) PDAC tumor lysate vaccines elicited strong antibody production against multiple tumor-associated antigens and activated multiple tumor-specific T cells. The lysate vaccines stimulated a robust immune response in animal models, resulting in tumor suppression and a significant improvement in survival without any adverse events.Conclusions
Our data suggest that α-gal(+) PDAC tumor lysate vaccination may be a practical and effective new immunotherapeutic approach for treating pancreatic cancer.
SUBMITTER: Furukawa K
PROVIDER: S-EPMC5659602 | biostudies-literature | 2017
REPOSITORIES: biostudies-literature
Furukawa Kenta K Tanemura Masahiro M Miyoshi Eiji E Eguchi Hidetoshi H Nagano Hiroaki H Matsunami Katsuyoshi K Nagaoka Satoshi S Yamada Daisaku D Asaoka Tadafumi T Noda Takehiro T Wada Hiroshi H Kawamoto Koichi K Goto Kunihito K Taniyama Kiyomi K Mori Masaki M Doki Yuichiro Y
PloS one 20171027 10
<h4>Objectives</h4>Single-agent immunotherapy is ineffective against poorly immunogenic cancers, including pancreatic ductal adenocarcinoma (PDAC). The aims of this study were to demonstrate the feasibility of production of novel autologous tumor lysate vaccines from resected PDAC tumors, and verify vaccine safety and efficacy.<h4>Methods</h4>Fresh surgically resected tumors obtained from human patients were processed to enzymatically synthesize α-gal epitopes on the carbohydrate chains of membr ...[more]