Pre-immunization of donor lymphocytes with GITR agonistic antibody enhances antitumor immunity in autologous hematopoietic stem cell transplantation.
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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Base de dados:
MEDLINE
Assunto principal:
Linfócitos
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Neoplasias do Colo
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Transplante de Células-Tronco Hematopoéticas
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Proteína Relacionada a TNFR Induzida por Glucocorticoide
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Anticorpos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article