start-ver=1.4 cd-journal=joma no-vol=62 cd-vols= no-issue=4 article-no= start-page=639 end-page=652 dt-received= dt-revised= dt-accepted= dt-pub-year=2013 dt-pub=201304 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Intratumoral peptide injection enhances tumor cell antigenicity recognized by cytotoxic T lymphocytes: a potential option for improvement in antigen-specific cancer immunotherapy en-subtitle= kn-subtitle= en-abstract= kn-abstract=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-3(144-152) (FVGEFFTDV) and cytomegalovirus(495-503) (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-3(144-152) and cytomegalovirus(495-503) 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 ovalbumin(257-264) 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. en-copyright= kn-copyright= en-aut-name=NobuokaDaisuke en-aut-sei=Nobuoka en-aut-mei=Daisuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YoshikawaToshiaki en-aut-sei=Yoshikawa en-aut-mei=Toshiaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=TakahashiMari en-aut-sei=Takahashi en-aut-mei=Mari kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=IwamaTatsuaki en-aut-sei=Iwama en-aut-mei=Tatsuaki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=HorieKazutaka en-aut-sei=Horie en-aut-mei=Kazutaka kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=ShimomuraManami en-aut-sei=Shimomura en-aut-mei=Manami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=SuzukiShiro en-aut-sei=Suzuki en-aut-mei=Shiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=SakemuraNoriko en-aut-sei=Sakemura en-aut-mei=Noriko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=NakatsugawaMunehide en-aut-sei=Nakatsugawa en-aut-mei=Munehide kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=SadamoriHiroshi en-aut-sei=Sadamori en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=YagiTakahito en-aut-sei=Yagi en-aut-mei=Takahito kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=FujiwaraToshiyoshi en-aut-sei=Fujiwara en-aut-mei=Toshiyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=NakatsuraTetsuya en-aut-sei=Nakatsura en-aut-mei=Tetsuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= affil-num=1 en-affil= kn-affil=Natl Canc Ctr Hosp East, Res Ctr Innovat Oncol, Div Canc Immunotherapy affil-num=2 en-affil= kn-affil=Natl Canc Ctr Hosp East, Res Ctr Innovat Oncol, Div Canc Immunotherapy affil-num=3 en-affil= kn-affil=Natl Canc Ctr Hosp East, Res Ctr Innovat Oncol, Div Canc Immunotherapy affil-num=4 en-affil= kn-affil=Natl Canc Ctr Hosp East, Res Ctr Innovat Oncol, Div Canc Immunotherapy affil-num=5 en-affil= kn-affil=Natl Canc Ctr Hosp East, Res Ctr Innovat Oncol, Div Canc Immunotherapy affil-num=6 en-affil= kn-affil=Natl Canc Ctr Hosp East, Res Ctr Innovat Oncol, Div Canc Immunotherapy affil-num=7 en-affil= kn-affil=Natl Canc Ctr Hosp East, Res Ctr Innovat Oncol, Div Canc Immunotherapy affil-num=8 en-affil= kn-affil=Natl Canc Ctr Hosp East, Res Ctr Innovat Oncol, Div Canc Immunotherapy affil-num=9 en-affil= kn-affil=Natl Canc Ctr Hosp East, Res Ctr Innovat Oncol, Div Canc Immunotherapy affil-num=10 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol affil-num=11 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol affil-num=12 en-affil= kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol affil-num=13 en-affil= kn-affil=Natl Canc Ctr Hosp East, Res Ctr Innovat Oncol, Div Canc Immunotherapy en-keyword=Intratumoral peptide injection kn-keyword=Intratumoral peptide injection en-keyword=Antigen kn-keyword=Antigen en-keyword=Immunotherapy kn-keyword=Immunotherapy en-keyword=Cytotoxic T lymphocyte kn-keyword=Cytotoxic T lymphocyte END