A new purification method for enhancing the immunogenicity of heat shock protein 70-peptide complexes.
Oncol Rep
; 28(6): 1977-83, 2012 Dec.
Article
en En
| MEDLINE
| ID: mdl-23007635
ABSTRACT
When purified from a tumor, certain heat shock protein 70 (HSP70)-peptide complexes (PCs) can function as effective vaccines against the tumor from which the complexes were isolated. The immunogenic mechanisms of HSP70 preparations imply that tumor-derived HSP70-PCs exhibit antigens associated with antigen-presenting cells such as dendritic cells (DCs), inducing antigen-specific cytotoxic CD8+ T cells. However, some important membrane-resident tumor-associated peptides, such as the HER-2/neu (c-erbB2) oncogenic protein, cannot be purified from HSP70 by traditional methods. In the present study, a new approach for the purification of HSP70-PCs from HER-2-overexpressing breast cancer cells was established. The detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) was used to obtain more effectual tumor peptides. The new purified product was named HSP70-HER-2-PC, and its immunological activities were determined. Traditionally purified HSP70-PCs (without CHAPS) and recombinant human HSP70-HER-2 protein complexes (recombined in vitro) were used as controls. These three HSP70-associated tumor antigenic complex pulsed dendritic cells (DCs) were used to stimulate an antitumor response. The mature DCs pulsed with HSP70-HER-2-PCs stimulated autologous T cells to secrete higher levels of type I cytokine compared to the two control groups. Moreover, DCs pulsed with HSP70-HER-2-PCs induced the most specific CD8+ T cells that specifically killed the same tumor cells. These findings provide a basis for new approaches in enhancing HSP70-based immunotherapy for HER-2-associated or other membrane antigenic peptide-related cancers.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Receptor ErbB-2
/
Proteínas HSP70 de Choque Térmico
/
Linfocitos T CD8-positivos
Límite:
Female
/
Humans
Idioma:
En
Revista:
Oncol Rep
Asunto de la revista:
NEOPLASIAS
Año:
2012
Tipo del documento:
Article