NY-ESO-1 is expressed in wide range of human malignancies expect testis in normal tissues and induces spontaneous antibody in patients with cancers expressing NY-ESO-1. Because of its unique expression and high immunogenicity, NY-ESO-1 is promising as a target of cancer vaccine. We have conducted serial clinical trials with the NY-ESO-1 protein since 2004 and antigen-specific immune responses were observed in most of patients immunized. Some patients showed feasible clinical responses however they were limited and novel immune modulators which could make NY-ESO-1 protein vaccination effective are needed. Recently, stimulation through the Toll-like receptors (TLRs) enhance the induction of antigen-specific immune responses upon cancer vaccine has become apparent. In this study, we conducted a phase I cancer vaccine clinical trial using NY-ESO-1 protein combined with Poly ICLC and Picibanil OK-432 as TLR 3 and 4 agonist, respectively.
This trial was designed to evaluate the safety, induction of immune response and clinical response. Patients with advanced cancers expressing NY-ESO-1 were eligible. 200μg NY-ESO-1 protein mixed with Montanide in combination of Poly ICLC and/or Picibanil OK-432 was administered subcutaneously once every 2 weeks in six times. Seven patients with esophageal cancer, three with gastric cancer, two with lung cancer, two with ovarian cancer and one with malignant melanoma were enrolled in four groups, i) NY-ESO-1 protein alone (n=3), ii) NY-ESO-1 protein with OK-432 (n=3), iii) NY-ESO-1 protein with Poly ICLC (n=3), iv) NY-ESO-1 protein with OK-432 and Poly ICLC (n=6). All patients developed an injection-site reaction and fever (grade1 or 2) but no severe adverse events related to the drug were observed. An increase in the NY-ESO-1 antibody response was observed in all patients after vaccination. Earlier induction and higher frequency of NY-ESO-1 responsible T cells were observed in patients immunized with Poly ICLC than those without Poly ICLC. NY-ESO-1 protein vaccine with Poly ICLC and OK432 was safe and antigen-specific immune responses were induced in all patients. TLR agonists would be useful and effective immune modulators for cancer vaccines.
Citation Format: Tomohira Takeoka, Hirotsugu Nagase, Yasuhiro Miyazaki, Tsuyoshi Takahashi, Yukinori Kurokawa, Tomoki Makino, Makoto Yamasaki, Shuji Takiguchi, Masaki Mori, Yuichiro Doki, Hisashi Wada. NY-ESO-1 protein cancer vaccine with TLR 3 and 4 agonists. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr A169.
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