ID | 50734 |
FullText URL | |
Author |
Nobuoka, Daisuke
Yoshikawa, Toshiaki
Takahashi, Mari
Iwama, Tatsuaki
Horie, Kazutaka
Shimomura, Manami
Suzuki, Shiro
Sakemura, Noriko
Nakatsugawa, Munehide
Nakatsura, Tetsuya
|
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.
|
Keywords | Intratumoral peptide injection
Antigen
Immunotherapy
Cytotoxic T lymphocyte
|
Published Date | 2013-04
|
Publication Title |
Cancer Immunology, Immunotherapy
|
Volume | volume62
|
Issue | issue4
|
Start Page | 639
|
End Page | 652
|
ISSN | 0340-7004
|
Content Type |
Journal Article
|
Official Url | http://dx.doi.org/10.1007/s00262-012-1366-6
|
Related Url | http://ousar.lib.okayama-u.ac.jp/metadata/50734
|
language |
English
|
File Version | publisher
|
Refereed |
True
|
DOI | |
Web of Science KeyUT |