TY - JOUR
T1 - Efficacy of the NCCV Cocktail-1 vaccine for refractory pediatric solid tumors
T2 - A phase I clinical trial
AU - Akazawa, Yu
AU - Hosono, Ako
AU - Yoshikawa, Toshiaki
AU - Kaneda, Hide
AU - Nitani, Chika
AU - Hara, Junichi
AU - Kinoshita, Yoshiaki
AU - Kohashi, Kenichi
AU - Manabe, Atsushi
AU - Fukutani, Miki
AU - Wakabayashi, Masashi
AU - Sato, Akihiro
AU - Shoda, Kayoko
AU - Shimomura, Manami
AU - Mizuno, Shoichi
AU - Nakamoto, Yasunari
AU - Nakatsura, Tetsuya
N1 - Funding Information:
We wish to thank OncoTherapy Science, SHIONOGI & Co., and Otsuka Pharmaceutical Co., which approved the use of KOC1, FOXM1, and KIF20A in this trial and provided a summary of investigational drugs for each peptide vaccine. We would also like to thank the members of the clinical trial support department of the National Cancer Hospital East, including A.S., M.W., and M.F., which coordinated this clinical trial. In addition, we thank Kenichi Yoshimura, who belongs to the Innovative Clinical Research Center, Kanazawa University, for supporting the case calculation for this trial. Finally, we would like to thank Editage for English language editing.
Publisher Copyright:
© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Pediatric refractory solid tumors are aggressive malignant diseases, resulting in an extremely poor prognosis. KOC1, FOXM1, and KIF20A are cancer antigens that could be ideal targets for anticancer immunotherapy against pediatric refractory solid tumors with positive expression for these antigens. This nonrandomized, open-label, phase I clinical trial evaluated the safety and efficacy of the NCCV Cocktail-1 vaccine, which is a cocktail of cancer peptides derived from KOC1, FOXM1, and KIF20A, in patients with pediatric refractory solid tumors. Twelve patients with refractory pediatric solid tumors underwent NCCV Cocktail-1 vaccination weekly by intradermal injections. The primary endpoint was the safety of the NCCV Cocktail-1 vaccination, and the secondary endpoints were the immune response, as measured by interferon-r enzyme-linked immunospot assay, and the clinical outcomes including tumor response and progression-free survival. The NCCV Cocktail-1 vaccine was well tolerated. The clinical response of this trial showed that 4 patients had stable disease after 8 weeks and 2 patients maintained remission for >11 months. In 4, 8, and 5 patients, the NCCV Cocktail-1 vaccine induced the sufficient number of peptide-specific CTLs for KOC1, FOXM1, and KIF20A, respectively. Patients with high peptide-specific CTL frequencies for KOC1, FOXM1, and KIF20A had better progression-free survival than those with low frequencies. The findings of this clinical trial showed that the NCCV Cocktail-1 vaccine could be a novel therapeutic strategy, with adequate effects against pediatric refractory solid tumors. Future large-scale trials should evaluate the efficacy of the NCCV Cocktail-1 vaccination.
AB - Pediatric refractory solid tumors are aggressive malignant diseases, resulting in an extremely poor prognosis. KOC1, FOXM1, and KIF20A are cancer antigens that could be ideal targets for anticancer immunotherapy against pediatric refractory solid tumors with positive expression for these antigens. This nonrandomized, open-label, phase I clinical trial evaluated the safety and efficacy of the NCCV Cocktail-1 vaccine, which is a cocktail of cancer peptides derived from KOC1, FOXM1, and KIF20A, in patients with pediatric refractory solid tumors. Twelve patients with refractory pediatric solid tumors underwent NCCV Cocktail-1 vaccination weekly by intradermal injections. The primary endpoint was the safety of the NCCV Cocktail-1 vaccination, and the secondary endpoints were the immune response, as measured by interferon-r enzyme-linked immunospot assay, and the clinical outcomes including tumor response and progression-free survival. The NCCV Cocktail-1 vaccine was well tolerated. The clinical response of this trial showed that 4 patients had stable disease after 8 weeks and 2 patients maintained remission for >11 months. In 4, 8, and 5 patients, the NCCV Cocktail-1 vaccine induced the sufficient number of peptide-specific CTLs for KOC1, FOXM1, and KIF20A, respectively. Patients with high peptide-specific CTL frequencies for KOC1, FOXM1, and KIF20A had better progression-free survival than those with low frequencies. The findings of this clinical trial showed that the NCCV Cocktail-1 vaccine could be a novel therapeutic strategy, with adequate effects against pediatric refractory solid tumors. Future large-scale trials should evaluate the efficacy of the NCCV Cocktail-1 vaccination.
KW - cytotoxic T lymphocyte
KW - NCCV Cocktail-1
KW - pediatric refractory solid tumor
KW - peptide vaccine
KW - phase I
UR - http://www.scopus.com/inward/record.url?scp=85075139948&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85075139948&partnerID=8YFLogxK
U2 - 10.1111/cas.14206
DO - 10.1111/cas.14206
M3 - Article
C2 - 31571332
AN - SCOPUS:85075139948
SN - 1347-9032
VL - 110
SP - 3650
EP - 3662
JO - Cancer science
JF - Cancer science
IS - 12
ER -
