PMID- 30813491
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 11
IP  - 2
DP  - 2019 Feb 24
TI  - Identification of Novel HLA Class II-Restricted Neoantigens Derived from Driver 
      Mutations.
LID - 10.3390/cancers11020266 [doi]
LID - 266
AB  - Neoantigens derived from tumor-specific genetic mutations might be suitable 
      targets for cancer immunotherapy because of their high immunogenicity. In the 
      current study, we evaluated the immunogenicity of 10 driver mutations that are 
      frequently expressed in various cancers using peripheral blood mononuclear cells 
      from healthy donors (n = 25). Of the 10 synthetic peptides (27-mer) derived from 
      these mutations, the six peptides from KRAS-G12D, KRAS-G12R, KRAS-G13D, 
      NRAS-Q61R, PIK3CA-H1047R, and C-Kit-D816V induced T cell responses, suggesting 
      that frequent driver mutations are not always less immunogenic. In particular, 
      immune responses to PIK3CA-H1047R, C-Kit-D816V, KRAS-G13D, and NRAS-Q61R were 
      observed in more than 10% of the donors. All six peptides induced human leukocyte 
      antigen (HLA) class II-restricted CD4(+) T cell responses; notably, PIK3CA-H1047R 
      contained at least two different CD4(+) T cell epitopes restricted to different HLA 
      class II alleles. In addition, PIK3CA-H1047R and C-Kit-D816V induced 
      antigen-specific CD8(+) T cells as well, indicating that they might contain both 
      HLA class I- and class II-restricted epitopes. Since the identified neoantigens 
      might be shared by patients with various types of cancers and are not easily lost 
      due to immune escape, they have the potential to be promising off-the-shelf 
      cancer immunotherapy targets in patients with the corresponding mutations.
FAU - Iiizumi, Susumu
AU  - Iiizumi S
AD  - Department of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, 
      2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa 241-8515, Japan. 
      iizumi_s@brightpathbio.com.
AD  - Research & Early Development Division, BrightPath Biotherapeutics Co., Ltd., 
      3-25-22 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan. 
      iizumi_s@brightpathbio.com.
FAU - Ohtake, Junya
AU  - Ohtake J
AD  - Department of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, 
      2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa 241-8515, Japan. 
      qsl.suivx2000@gmail.com.
FAU - Murakami, Naoko
AU  - Murakami N
AD  - Department of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, 
      2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa 241-8515, Japan. 
      n.murakami_0131v2@outlook.jp.
AD  - Research & Early Development Division, BrightPath Biotherapeutics Co., Ltd., 
      3-25-22 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan. 
      n.murakami_0131v2@outlook.jp.
FAU - Kouro, Taku
AU  - Kouro T
AD  - Department of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, 
      2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa 241-8515, Japan. 
      kourot@gancen.asahi.yokohama.jp.
FAU - Kawahara, Mamoru
AU  - Kawahara M
AD  - Department of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, 
      2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa 241-8515, Japan. 
      mmrkawahara@gancen.asahi.yokohama.jp.
FAU - Isoda, Fumiko
AU  - Isoda F
AD  - Department of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, 
      2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa 241-8515, Japan. 
      isoda_f@brightpathbio.com.
AD  - Research & Early Development Division, BrightPath Biotherapeutics Co., Ltd., 
      3-25-22 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan. 
      isoda_f@brightpathbio.com.
FAU - Hamana, Hiroshi
AU  - Hamana H
AD  - Department of Innovative Cancer Immunotherapy, Graduate School of Medicine and 
      Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, 
      Japan. hamana@med.u-toyama.ac.jp.
FAU - Kishi, Hiroyuki
AU  - Kishi H
AD  - Department of Immunology, Graduate School of Medicine and Pharmaceutical 
      Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan. 
      immkishi@med.u-toyama.ac.jp.
FAU - Nakamura, Norihiro
AU  - Nakamura N
AD  - Research & Early Development Division, BrightPath Biotherapeutics Co., Ltd., 
      3-25-22 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan. 
      nakamura_n@brightpathbio.com.
FAU - Sasada, Tetsuro
AU  - Sasada T
AD  - Department of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, 
      2-3-2 Nakao, Asahi-ku, Yokohama, Kanagawa 241-8515, Japan. tsasada@kcch.jp.
LA  - eng
GR  - 26293293 and 17H04278/Japan Society for the Promotion of Science/
PT  - Journal Article
DEP - 20190224
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC6406322
OTO - NOTNLM
OT  - MHC class II epitope
OT  - driver mutation
OT  - neoantigen
COIS- S.I., N.M., and F.I. are full time employees of Brightpath Biotherapeutics Co., 
      Ltd. N.N. is the CSO of Brightpath Biotherapeutics Co., Ltd. This work was 
      supported in part by Brightpath Biotherapeutics Co., Ltd. The other authors 
      declare no conflicts of interest.
EDAT- 2019/03/01 06:00
MHDA- 2019/03/01 06:01
PMCR- 2019/02/24
CRDT- 2019/03/01 06:00
PHST- 2019/01/31 00:00 [received]
PHST- 2019/02/18 00:00 [revised]
PHST- 2019/02/20 00:00 [accepted]
PHST- 2019/03/01 06:00 [entrez]
PHST- 2019/03/01 06:00 [pubmed]
PHST- 2019/03/01 06:01 [medline]
PHST- 2019/02/24 00:00 [pmc-release]
AID - cancers11020266 [pii]
AID - cancers-11-00266 [pii]
AID - 10.3390/cancers11020266 [doi]
PST - epublish
SO  - Cancers (Basel). 2019 Feb 24;11(2):266. doi: 10.3390/cancers11020266.