TY - JOUR
T1 - Phase I clinical trial of a five-peptide cancer vaccine combined with cyclophosphamide in advanced solid tumors
AU - Murahashi, Mutsunori
AU - Hijikata, Yasuki
AU - Yamada, Kazunari
AU - Tanaka, Yoshihiro
AU - Kishimoto, Junji
AU - Inoue, Hiroyuki
AU - Marumoto, Tomotoshi
AU - Takahashi, Atsushi
AU - Okazaki, Toshihiko
AU - Takeda, Kazuyoshi
AU - Hirakawa, Masakazu
AU - Fujii, Hiroshi
AU - Okano, Shinji
AU - Morita, Masaru
AU - Baba, Eishi
AU - Mizumoto, Kazuhiro
AU - Maehara, Yoshihiko
AU - Tanaka, Masao
AU - Akashi, Koichi
AU - Nakanishi, Yoichi
AU - Yoshida, Koji
AU - Tsunoda, Takuya
AU - Tamura, Kazuo
AU - Nakamura, Yusuke
AU - Tani, Kenzaburo
N1 - Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - We designed a phase I trial to investigate the safety, immune responses and clinical benefits of a five-peptide cancer vaccine in combination with chemotherapy. Study subjects were patients positive for HLA-A2402 with locally advanced, metastatic, and/or recurrent gastrointestinal, lung or cervical cancer. Eighteen patients including nine cases of colorectal cancer were treated with escalating doses of cyclophosphamide 4 days before vaccination. Five HLA-A2402-restricted, tumor-associated antigen (TAA) epitope peptides from KOC1, TTK, URLC10, DEPDC1 and MPHOSPH1 were injected weekly for 4 weeks. Treatment was well tolerated without any adverse events above grade 3. Analysis of peripheral blood lymphocytes showed that the number of regulatory T cells dropped from baseline after administration of cyclophosphamide and confirmed that TAA-specific T cell responses were associated significantly with longer overall survival. This phase I clinical trial demonstrated safety and promising immune responses that correlated with vaccine-induced T-cell responses. Therefore, this approach warrants further clinical studies.
AB - We designed a phase I trial to investigate the safety, immune responses and clinical benefits of a five-peptide cancer vaccine in combination with chemotherapy. Study subjects were patients positive for HLA-A2402 with locally advanced, metastatic, and/or recurrent gastrointestinal, lung or cervical cancer. Eighteen patients including nine cases of colorectal cancer were treated with escalating doses of cyclophosphamide 4 days before vaccination. Five HLA-A2402-restricted, tumor-associated antigen (TAA) epitope peptides from KOC1, TTK, URLC10, DEPDC1 and MPHOSPH1 were injected weekly for 4 weeks. Treatment was well tolerated without any adverse events above grade 3. Analysis of peripheral blood lymphocytes showed that the number of regulatory T cells dropped from baseline after administration of cyclophosphamide and confirmed that TAA-specific T cell responses were associated significantly with longer overall survival. This phase I clinical trial demonstrated safety and promising immune responses that correlated with vaccine-induced T-cell responses. Therefore, this approach warrants further clinical studies.
KW - Cyclophosphamide
KW - Five-peptide cancer vaccine
KW - Regulatory T cells
KW - Translational research
UR - http://www.scopus.com/inward/record.url?scp=84964600396&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84964600396&partnerID=8YFLogxK
U2 - 10.1016/j.clim.2016.03.015
DO - 10.1016/j.clim.2016.03.015
M3 - Article
C2 - 27072896
AN - SCOPUS:84964600396
SN - 1521-6616
VL - 166-167
SP - 48
EP - 58
JO - Clinical Immunology
JF - Clinical Immunology
ER -
