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Pre-immunization of donor lymphocytes with GITR agonistic antibody enhances antitumor immunity in autologous hematopoietic stem cell transplantation.
Henmi, Marina; Shibasaki, Chihiro; Mizoguchi, Yukihiro; Hirata, Aya; Sawai, Eri; Narumi, Kenta; Aoki, Kazunori.
Afiliação
  • Henmi M; Department of Immune Medicine, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
  • Shibasaki C; Department of Immune Medicine, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
  • Mizoguchi Y; Department of Immune Medicine, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
  • Hirata A; Department of Immune Medicine, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
  • Sawai E; Department of Immune Medicine, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
  • Narumi K; Department of Immune Medicine, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
  • Aoki K; Department of Immune Medicine, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. Electronic address: kaoki@ncc.go.jp.
Biochem Biophys Res Commun ; 509(1): 96-101, 2019 01 29.
Article em En | MEDLINE | ID: mdl-30579597
ABSTRACT
The lymphopenic condition following autologous hematopoietic stem cell transplantation (HSCT) enhances the proliferation of T cells by engaging tumor-associated antigens, leading to the alteration of the T-cell repertoire towards antitumor immunity. However, cure by autologous HSCT alone have rarely occurred in the clinical setting. Since tumor-reactive lymphocytes preferentially proliferate during reconstitution of the immune system, we examined whether the priming of donor lymphocytes can strengthen the antitumor effect by HSCT in a CT26 murine colon cancer model. The systemic administration of an anti-glucocorticoid-induced TNF receptor (GITR) agonistic antibody (Ab) significantly increased the number of CT26-responsive T cells but not that of auto-reactive lymphocytes in donor mice. The infusion of non-primed and GITR Ab-primed donor lymphocytes suppressed the CT26 tumor growth, and only the primed lymphocytes eliminated tumors in all the treated mice. The frequency of CT26-responsive T cells was elevated in recipient mice infused with both primed and non-primed lymphocytes until 4 weeks after transplantation, while the frequency in recipients with primed lymphocytes was markedly elevated compared with that in mice harboring non-primed lymphocytes at 2 weeks. The frequencies of regulatory T cells and myeloid-derived suppressor cells were elevated in recipient mice infused with primed and non-primed lymphocytes 2 weeks after transplantation, and returned to normal levels by week 4. The combination of autologous HSCT with pre-immunization of donor lymphocytes is a promising strategy to induce strong antitumor immunity.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos / Neoplasias do Colo / Transplante de Células-Tronco Hematopoéticas / Proteína Relacionada a TNFR Induzida por Glucocorticoide / Anticorpos Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos / Neoplasias do Colo / Transplante de Células-Tronco Hematopoéticas / Proteína Relacionada a TNFR Induzida por Glucocorticoide / Anticorpos Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article