PMID- 23143746
OWN - NLM
STAT- MEDLINE
DCOM- 20130607
LR  - 20211021
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Print)
IS  - 0340-7004 (Linking)
VI  - 62
IP  - 4
DP  - 2013 Apr
TI  - Intratumoral peptide injection enhances tumor cell antigenicity recognized by 
      cytotoxic T lymphocytes: a potential option for improvement in antigen-specific 
      cancer immunotherapy.
PG  - 639-52
LID - 10.1007/s00262-012-1366-6 [doi]
AB  - Antigen-specific cancer immunotherapy is a promising strategy for improving 
      cancer treatment. Recently, many tumor-associated antigens and their epitopes 
      recognized by cytotoxic T lymphocytes (CTLs) have been identified. However, the 
      density of endogenously presented antigen-derived peptides on tumor cells is 
      generally sparse, resulting in the inability of antigen-specific CTLs to work 
      effectively. We hypothesize that increasing the density of an antigen-derived 
      peptide would enhance antigen-specific cancer immunotherapy. Here, we 
      demonstrated that intratumoral peptide injection leads to additional peptide 
      loading onto major histocompatibility complex class I molecules of tumor cells, 
      enhancing tumor cell recognition by antigen-specific CTLs. In in vitro studies, 
      human leukocyte antigen (HLA)-A*02:01-restricted glypican-3144-152 (FVGEFFTDV) 
      and cytomegalovirus495-503 (NLVPMVATV) peptide-specific CTLs showed strong 
      activity against all peptide-pulsed cell lines, regardless of whether the tumor 
      cells expressed the antigen. In in vivo studies using immunodeficient mice, 
      glypican-3144-152 and cytomegalovirus495-503 peptides injected into a solid mass 
      were loaded onto HLA class I molecules of tumor cells. In a peptide vaccine model 
      and an adoptive cell transfer model using C57BL/6 mice, intratumoral injection of 
      ovalbumin257-264 peptide (SIINFEKL) was effective for tumor growth inhibition and 
      survival against ovalbumin-negative tumors without adverse reactions. Moreover, 
      we demonstrated an antigen-spreading effect that occurred after intratumoral 
      peptide injection. Intratumoral peptide injection enhances tumor cell 
      antigenicity and may be a useful option for improvement in antigen-specific 
      cancer immunotherapy against solid tumors.
FAU - Nobuoka, Daisuke
AU  - Nobuoka D
AD  - Division of Cancer Immunotherapy, Research Center for Innovative Oncology, 
      National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, 277-8577, 
      Japan.
FAU - Yoshikawa, Toshiaki
AU  - Yoshikawa T
FAU - Takahashi, Mari
AU  - Takahashi M
FAU - Iwama, Tatsuaki
AU  - Iwama T
FAU - Horie, Kazutaka
AU  - Horie K
FAU - Shimomura, Manami
AU  - Shimomura M
FAU - Suzuki, Shiro
AU  - Suzuki S
FAU - Sakemura, Noriko
AU  - Sakemura N
FAU - Nakatsugawa, Munehide
AU  - Nakatsugawa M
FAU - Sadamori, Hiroshi
AU  - Sadamori H
FAU - Yagi, Takahito
AU  - Yagi T
FAU - Fujiwara, Toshiyoshi
AU  - Fujiwara T
FAU - Nakatsura, Tetsuya
AU  - Nakatsura T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121111
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-A Antigens)
RN  - 0 (Peptide Fragments)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Colonic Neoplasms/immunology/therapy
MH  - Epitopes, T-Lymphocyte/*immunology
MH  - Female
MH  - HLA-A Antigens/*immunology
MH  - Hep G2 Cells
MH  - Humans
MH  - Immunotherapy/*methods
MH  - Injections, Intralesional
MH  - Liver Neoplasms/immunology/therapy
MH  - Lymphoma/immunology/therapy
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Mice, Transgenic
MH  - Peptide Fragments/*administration & dosage/*immunology
MH  - T-Lymphocytes, Cytotoxic/*immunology
PMC - PMC3624010
COIS- The authors declare that they have no conflicts of interest.
EDAT- 2012/11/13 06:00
MHDA- 2013/06/08 06:00
PMCR- 2012/11/11
CRDT- 2012/11/13 06:00
PHST- 2012/06/29 00:00 [received]
PHST- 2012/10/29 00:00 [accepted]
PHST- 2012/11/13 06:00 [entrez]
PHST- 2012/11/13 06:00 [pubmed]
PHST- 2013/06/08 06:00 [medline]
PHST- 2012/11/11 00:00 [pmc-release]
AID - 1366 [pii]
AID - 10.1007/s00262-012-1366-6 [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2013 Apr;62(4):639-52. doi: 10.1007/s00262-012-1366-6. 
      Epub 2012 Nov 11.