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Intratumoral peptide injection enhances tumor cell antigenicity recognized by cytotoxic T lymphocytes: a potential option for improvement in antigen-specific cancer immunotherapy.
Nobuoka, Daisuke; Yoshikawa, Toshiaki; Takahashi, Mari; Iwama, Tatsuaki; Horie, Kazutaka; Shimomura, Manami; Suzuki, Shiro; Sakemura, Noriko; Nakatsugawa, Munehide; Sadamori, Hiroshi; Yagi, Takahito; Fujiwara, Toshiyoshi; Nakatsura, Tetsuya.
Afiliação
  • Nobuoka D; Division of Cancer Immunotherapy, Research Center for Innovative Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, 277-8577, Japan.
Cancer Immunol Immunother ; 62(4): 639-52, 2013 Apr.
Article em En | MEDLINE | ID: mdl-23143746
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*0201-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.
Assuntos

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Fragmentos de Peptídeos / Linfócitos T Citotóxicos / Antígenos HLA-A / Epitopos de Linfócito T / Imunoterapia Limite: Animals / Female / Humans Idioma: En Revista: Cancer Immunol Immunother Assunto da revista: ALERGIA E IMUNOLOGIA / NEOPLASIAS / TERAPEUTICA Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Bases de dados: MEDLINE Assunto principal: Fragmentos de Peptídeos / Linfócitos T Citotóxicos / Antígenos HLA-A / Epitopos de Linfócito T / Imunoterapia Limite: Animals / Female / Humans Idioma: En Revista: Cancer Immunol Immunother Assunto da revista: ALERGIA E IMUNOLOGIA / NEOPLASIAS / TERAPEUTICA Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Japão