Combination GITR targeting/PD-1 blockade with vaccination drives robust antigen-specific antitumor immunity.
Oncotarget
; 8(24): 39117-39130, 2017 Jun 13.
Article
en En
| MEDLINE
| ID: mdl-28388572
ABSTRACT
Tumor progression is facilitated immunologically by mechanisms that include low antigen expression, an absence of coimmunostimulatory signals, and the presence of regulatory T cells (Tregs), all of which act to suppress and restrict effector T cells in the tumor. It may be possible to overcome these conditions by a combination of modulatory immunotherapy agents and tumor-antigen targeting to activate and drive effective antitumor T cell responses. Here, we demonstrated that co-administration of aGITR and aPD-1 monoclonal antibodies (mAb) in combination with a peptide vaccine (Vax) in mice bearing established tumors significantly delayed tumor growth and induced complete regression in 50% of the mice. This response was associated with increased expansion and functionality of potent Ag-specific polyfunctional CD8+ T cells, reduced Tregs, and the generation of memory T cells. Tumor regression correlated with the expansion of tumor-infiltrating antigen-specific CD8+ effector memory T cells, as depletion of this cell population significantly reduced the effectiveness of the triple combination Vax/aGITR/aPD-1 therapy. These findings support the concept that dual aGITR/aPD-1 combination with cancer vaccines may be a novel strategy against poorly immunogenic tumors.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
2_ODS3
/
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
2_enfermedades_transmissibles
/
6_malignant_skin_melanoma
Asunto principal:
Melanoma Experimental
/
Linfocitos T Reguladores
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Vacunas contra el Cáncer
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Proteína Relacionada con TNFR Inducida por Glucocorticoide
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Receptor de Muerte Celular Programada 1
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Anticuerpos Monoclonales
/
Antígenos de Neoplasias
Límite:
Animals
Idioma:
En
Revista:
Oncotarget
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos