RRC ID |
64051
|
著者 |
Nobuoka D, Yoshikawa T, Takahashi M, Iwama T, Horie K, Shimomura M, Suzuki S, Sakemura N, Nakatsugawa M, Sadamori H, Yagi T, Fujiwara T, Nakatsura T.
|
タイトル |
Intratumoral peptide injection enhances tumor cell antigenicity recognized by cytotoxic T lymphocytes: a potential option for improvement in antigen-specific cancer immunotherapy.
|
ジャーナル |
Cancer Immunol Immunother
|
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-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.
|
巻・号 |
62(4)
|
ページ |
639-52
|
公開日 |
2013-4-1
|
DOI |
10.1007/s00262-012-1366-6
|
PMID |
23143746
|
PMC |
PMC3624010
|
MeSH |
Animals
Cell Line, Tumor
Colonic Neoplasms / immunology
Colonic Neoplasms / therapy
Epitopes, T-Lymphocyte / immunology*
Female
HLA-A Antigens / immunology*
Hep G2 Cells
Humans
Immunotherapy / methods*
Injections, Intralesional
Liver Neoplasms / immunology
Liver Neoplasms / therapy
Lymphoma / immunology
Lymphoma / therapy
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred NOD
Mice, SCID
Mice, Transgenic
Peptide Fragments / administration & dosage*
Peptide Fragments / immunology*
T-Lymphocytes, Cytotoxic / immunology*
|
IF |
5.442
|
リソース情報 |
ヒト・動物細胞 |
T2(RCB1932) |