Single-chain antigen recognition receptors that costimulate potent rejection of established experimental tumors.
Blood
; 100(9): 3155-63, 2002 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-12384413
ABSTRACT
Tumor cells are usually weakly immunogenic as they largely express self-antigens and can down-regulate major histocompatability complex/peptide molecules and critical costimulatory ligands. The challenge for immunotherapies has been to provide vigorous immune effector cells that circumvent these tumor escape mechanisms and eradicate established tumors. One promising approach is to engineer T cells with single-chain antibody receptors, and since T cells require 2 distinct signals for optimal activation, we have compared the therapeutic efficacy of erbB2-reactive chimeric receptors that contain either T-cell receptor zeta (TCR-zeta) or CD28/TCR-zeta signaling domains. We have demonstrated that primary mouse CD8(+) T lymphocytes expressing the single-chain Fv (scFv)-CD28-zeta receptor have a greater capacity to secrete Tc1 cytokines, induce T-cell proliferation, and inhibit established tumor growth and metastases in vivo. The suppression of established tumor burden by cytotoxic T cells expressing the CD28/TCR-zeta chimera was critically dependent upon their interferon gamma (IFN-gamma) secretion. Our study has illustrated the practical advantage of engineering a T-cell signaling complex that codelivers CD28 activation, dependent only upon the tumor's expression of the appropriate tumor associated antigen.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Região Variável de Imunoglobulina
/
Fragmentos de Imunoglobulinas
/
Ativação Linfocitária
/
Receptores de Antígenos de Linfócitos T
/
Linfócitos T Citotóxicos
/
Interferon gama
/
Antígenos CD28
/
Receptor ErbB-2
/
Proteínas de Membrana
/
Antígenos de Neoplasias
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article