Furukawa Kenta, Tanemura Masahiro, Miyoshi Eiji, Eguchi Hidetoshi, Nagano Hiroaki, Matsunami Katsuyoshi, Nagaoka Satoshi, Yamada Daisaku, Asaoka Tadafumi, Noda Takehiro, Wada Hiroshi, Kawamoto Koichi, Goto Kunihito, Taniyama Kiyomi, Mori Masaki, Doki Yuichiro
Department of Gastroenterological Surgery, Osaka Police Hospital, Osaka, Japan.
Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Osaka, Japan.
PLoS One. 2017 Oct 27;12(10):e0184901. doi: 10.1371/journal.pone.0184901. eCollection 2017.
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.
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.
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.
Our data suggest that α-gal(+) PDAC tumor lysate vaccination may be a practical and effective new immunotherapeutic approach for treating pancreatic cancer.
单药免疫疗法对包括胰腺导管腺癌（PDAC）在内的免疫原性较差的癌症无效。本研究的目的是证明从切除的PDAC肿瘤中制备新型自体肿瘤裂解物疫苗的可行性，并验证疫苗的安全性和有效性。
对从人类患者手术切除的新鲜肿瘤进行处理，以在膜糖蛋白的碳水化合物链上酶促合成α-半乳糖表位。分析处理后的膜上α-半乳糖表位的表达和抗Gal的结合情况，并在体外和体内评估疫苗的疗效。
对来自10名不同患者的PDAC肿瘤裂解物进行处理后，证明有效合成了α-半乳糖表位，并且肿瘤裂解物能轻易结合抗Gal单克隆抗体。α-半乳糖（+）PDAC肿瘤裂解物疫苗引发了针对多种肿瘤相关抗原的强烈抗体产生，并激活了多种肿瘤特异性T细胞。裂解物疫苗在动物模型中刺激了强大的免疫反应，导致肿瘤抑制和生存期显著改善，且无任何不良事件。
我们的数据表明，α-半乳糖（+）PDAC肿瘤裂解物疫苗接种可能是一种治疗胰腺癌的实用且有效的新免疫治疗方法。
