TY - JOUR
T1 - NY-ESO-1 Protein Cancer Vaccine with Poly-ICLC and OK-432
T2 - Rapid and Strong Induction of NY-ESO-1-specific Immune Responses by Poly-ICLC
AU - Takeoka, Tomohira
AU - Nagase, Hirotsugu
AU - Kurose, Koji
AU - Ohue, Yoshihiro
AU - Yamasaki, Makoto
AU - Takiguchi, Shuji
AU - Sato, Eiichi
AU - Isobe, Midori
AU - Kanazawa, Takayuki
AU - Matsumoto, Mitsunobu
AU - Iwahori, Kota
AU - Kawashima, Atsunari
AU - Morimoto-Okazawa, Akiko
AU - Nishikawa, Hiroyoshi
AU - Oka, Mikio
AU - Pan, Linda
AU - Venhaus, Ralph
AU - Nakayama, Eiichi
AU - Mori, Masaki
AU - Doki, Yuichiro
AU - Wada, Hisashi
N1 - Funding Information:
Supported by a Grant-in-Aid for Scientific Research (B) and the Project for Development of Innovative Research on Cancer Therapeutics (P-DIRECT) of Ministry of Education, Culture Sports Science and Technology of Japan and the Practice Research for Innovative Cancer Control from the Japan Agency for Medical Research and Development, AMED. The Investigational Agents for this study were supplied by the Ludwig Institute for Cancer Research and the Cancer Research Institute
Publisher Copyright:
© 2017 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2017
Y1 - 2017
N2 - We conducted a clinical trial of a cancer vaccine using NY-ESO-1 protein with polyinosinic-polycytidylic acid-poly-l-lysine carboxymethylcellulose (poly-ICLC) and/or OK-432 against solid tumors. A total of 15 patients were sequentially enrolled in 4 cohorts. Patients in cohort 1 received NY-ESO-1 protein; cohort 2a received NY-ESO-1 protein+OK-432; cohort 2b received NY-ESO-1 protein+poly-ICLC; cohort 3 received NY-ESO-1 protein+OK-432+poly-ICLC with Montanide ISA-51. The endpoints of this trial were safety, NY-ESO-1 immune responses, and clinical response. Vaccine-related adverse events observed were fever and injection-site reaction (grade 1). Two patients showed stable disease after vaccination. NY-ESO-1 antibodies were observed in 4 patients at the baseline (sero-positive) and augmented in all patients after vaccination. Eleven patients showed a conversion of negative antibody responses at baseline to positive after vaccination (seroconversion). The seroconversions were observed in all 11 sero-negative patients by the fourth immunization; in particular, it was observed by the second immunization in patients with poly-ICLC, and these induced antibody responses were stronger than those in patients immunized without poly-ICLC. The number of NY-ESO-1-specific interferon (IFN)γ-producing T cells was increased in patients immunized with poly-ICLC and/or OK-432, and furthermore, the increase of IFNγ-producing CD8 T cells in patients immunized with poly-ICLC was significantly higher than that in patients without poly-ICLC. Nonspecific activations of T-cell or antigen presenting cells were not observed. Our present study showed that poly-ICLC is a promising adjuvant for cancer vaccines.
AB - We conducted a clinical trial of a cancer vaccine using NY-ESO-1 protein with polyinosinic-polycytidylic acid-poly-l-lysine carboxymethylcellulose (poly-ICLC) and/or OK-432 against solid tumors. A total of 15 patients were sequentially enrolled in 4 cohorts. Patients in cohort 1 received NY-ESO-1 protein; cohort 2a received NY-ESO-1 protein+OK-432; cohort 2b received NY-ESO-1 protein+poly-ICLC; cohort 3 received NY-ESO-1 protein+OK-432+poly-ICLC with Montanide ISA-51. The endpoints of this trial were safety, NY-ESO-1 immune responses, and clinical response. Vaccine-related adverse events observed were fever and injection-site reaction (grade 1). Two patients showed stable disease after vaccination. NY-ESO-1 antibodies were observed in 4 patients at the baseline (sero-positive) and augmented in all patients after vaccination. Eleven patients showed a conversion of negative antibody responses at baseline to positive after vaccination (seroconversion). The seroconversions were observed in all 11 sero-negative patients by the fourth immunization; in particular, it was observed by the second immunization in patients with poly-ICLC, and these induced antibody responses were stronger than those in patients immunized without poly-ICLC. The number of NY-ESO-1-specific interferon (IFN)γ-producing T cells was increased in patients immunized with poly-ICLC and/or OK-432, and furthermore, the increase of IFNγ-producing CD8 T cells in patients immunized with poly-ICLC was significantly higher than that in patients without poly-ICLC. Nonspecific activations of T-cell or antigen presenting cells were not observed. Our present study showed that poly-ICLC is a promising adjuvant for cancer vaccines.
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U2 - 10.1097/CJI.0000000000000162
DO - 10.1097/CJI.0000000000000162
M3 - Article
C2 - 28338507
AN - SCOPUS:85016070544
SN - 1524-9557
VL - 40
SP - 140
EP - 147
JO - Journal of Biological Response Modifiers
JF - Journal of Biological Response Modifiers
IS - 4
ER -
