Adoptive transfer of chimeric FcepsilonRI gene-modified human T cells for cancer immunotherapy.
Hum Gene Ther
; 17(11): 1134-43, 2006 Nov.
Article
em En
| MEDLINE
| ID: mdl-17052145
ABSTRACT
Immunotherapeutic approaches involving genetic modification of T cells show promise in generating highly specific tumor-reactive effector cells for cancer treatment. Given the high affinity of FcRI (the subtype I Fc receptor for IgE) for IgE monoclonal antibody (mAb), modification of T cells with chimeric FcRI in combination with tumor-specific IgE mAbs is potentially a powerful and effective strategy to specifically target T cells to tumor cells. In this study, we retrovirally transduce human primary T cells with a cDNA encoding the extracellular domain of FcRI linked to the hinge and transmembrane domains of FcRI and the cytoplasmic domains of CD28 and T cell receptor zeta chain (FcRI-CD28-zeta). We demonstrate that human T cells expressing FcRI-CD28-zeta, in the presence of tumor-specific IgE mAb recognizing mouse CD8 antigen (Ly- 2.1+), can specifically secrete cytokine, proliferate, and mediate cytotoxic function after antigen ligation. Furthermore, adoptive transfer of FcRI-CD28-zeta cells incubated with anti-Ly-2.1 IgE mAb significantly enhances the survival of irradiated nonobese diabetic-severe combined immunodeficiency mice bearing Ly-2.1+ tumor compared with control mice. Thus, this set of experiments demonstrates that Fc gene-engineered human T cells mediate effector function in vitro and in vivo in an IgE-dependent manner and thus a novel and valid approach for cancer therapy can now be further developed.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Timoma
/
Linfócitos T
/
Receptores de IgE
/
Vacinas Anticâncer
/
Transferência Adotiva
/
Imunoterapia
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Hum Gene Ther
Assunto da revista:
GENETICA MEDICA
/
TERAPEUTICA
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Austrália