Peptide vaccination after T-cell transfer causes massive clonal expansion, tumor eradication, and manageable cytokine storm.
Cancer Res
; 70(21): 8339-46, 2010 Nov 01.
Article
en En
| MEDLINE
| ID: mdl-20940397
ABSTRACT
Adoptive T-cell transfer (ACT) is successfully applied as a cancer treatment that is based on the activation and effector functions of tumor-specific T cells. Here, we present results from a mouse model in which ACT is combined with a long peptide-based vaccine comprising gp100 T-cell epitopes. Transferred CD8(+) T cells expanded up to 1,000-fold after peptide vaccination, leading to a 3-fold increase in white blood cell count and a very high frequency in the generation of antigen-specific memory T cells, the generation of which tended to correlate with effective antitumor responses. An enormous pool of effector T cells spread widely to different tissues, including the skin and the immune-privileged eye, where they mediate tumor eradication. Importantly, these striking T-cell dynamics occurred in immunocompetent mice without prior hematologic conditioning. Continued activation of the specific T-cell pool by vaccination led to strong T-cell-mediated cytokine storm and lethality due to multi-organ failure. However, this immunopathology could be prevented by controlling the rapid biodistribution of the peptide or by using a weakly agonistic peptide. Together, these results identify a peptide vaccination strategy that can potently accentuate effective ACT in non-lymphodepleted hosts.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
/
Melanoma Experimental
/
Citocinas
/
Inmunoterapia Adoptiva
/
Linfocitos T CD8-positivos
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Epítopos de Linfocito T
/
Vacunas contra el Cáncer
/
Antígeno gp100 del Melanoma
Tipo de estudio:
Etiology_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cancer Res
Año:
2010
Tipo del documento:
Article
País de afiliación:
Países Bajos