Efficacy of the NCCV Cocktail-1 vaccine for refractory pediatric solid tumors: A phase I clinical trial

被引：8

作者：

Akazawa, Yu ^{[1
,2
]}

Hosono, Ako ^{[3
]}

Yoshikawa, Toshiaki ^{[1
]}

Kaneda, Hide ^{[4
]}

Nitani, Chika ^{[5
]}

Hara, Junichi ^{[5
]}

Kinoshita, Yoshiaki ^{[6
]}

Kohashi, Kenichi ^{[7
]}

Manabe, Atsushi ^{[8
]}

Fukutani, Miki ^{[9
]}

Wakabayashi, Masashi ^{[9
]}

Sato, Akihiro ^{[9
]}

Shoda, Kayoko ^{[1
]}

Shimomura, Manami ^{[1
]}

Mizuno, Shoichi ^{[1
]}

Nakamoto, Yasunari ^{[2
]}

Nakatsura, Tetsuya ^{[1
]}

机构：

[1] Natl Canc Ctr, Div Canc Immunotherapy, Exploratory Oncol Res & Clin Trial Ctr, Kashiwa, Chiba, Japan

[2] Univ Fukui, Fac Med Sci, Dept Internal Med 2, Eiheiji, Japan

[3] Natl Canc Ctr Hosp East, Div Pediat Oncol, Kashiwa, Chiba, Japan

[4] Natl Canc Ctr, Div Pediat Oncol, Tokyo, Japan

[5] Osaka City Gen Hosp, Dept Pediat Hematol & Oncol, Osaka, Japan

[6] Kyushu Univ Hosp, Dept Pediat Surg, Fukuoka, Fukuoka, Japan

[7] Kyushu Univ, Grad Sch Med Sci, Dept Anat Pathol, Fukuoka, Fukuoka, Japan

[8] Hokkaido Univ, Dept Pediat, Sapporo, Hokkaido, Japan

[9] Natl Canc Ctr Hosp East, Clin Res Support Off, Kashiwa, Chiba, Japan

来源：

CANCER SCIENCE | 2019年 / 110卷 / 12期

关键词：

cytotoxic T lymphocyte; NCCV Cocktail-1; pediatric refractory solid tumor; peptide vaccine; phase I; CHILDHOOD-CANCER; PROGNOSTIC-FACTORS; PEPTIDE VACCINE; ONCOLOGY; IMMUNOTHERAPY; CHILDREN; PROLIFERATION; RECEPTOR; SARCOMA; RISK;

D O I：

10.1111/cas.14206

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：3650 / 3662

页数：13

共 52 条

[1] Aging and Risk of Severe, Disabling, Life-Threatening, and Fatal Events in the Childhood Cancer Survivor Study [J].