Bypassing tumor-specific and bispecific antibodies: triggering of antitumor immunity by expression of anti-FcgammaR scFv on cancer cell surface.
Gene Ther
; 8(22): 1721-8, 2001 Nov.
Article
em En
| MEDLINE
| ID: mdl-11892840
ABSTRACT
We have developed a novel immunostimulatory molecule against tumor cells, composed of an anti-FcgammaRIII (CD16) scFv fused to the platelet-derived growth factor receptor (PDGFR) transmembrane region. This fusion molecule was stably expressed on the tumor cell surface and retained the ability of the parental antibody to bind soluble CD16. Tumor cells expressing anti-CD16 scFv triggered the release of IL-2 by Jurkat-CD 16/gamma cells and of TNFalpha by monocytes when co-cultured with these cells. Furthermore, NK cells could kill scFv-transfected HLA+ class I H1299 lung carcinoma tumor cells, but not the parental cells, indicating that anti-CD16 scFv tumor expression prevents the killer inhibitory receptor (KIR)-mediated inhibition of NK cell cytotoxicity. This anti-CD16 scFv tumor expression also enhanced tumor phagocytosis by IFNgamma-activated macrophages, a mechanism known to induce a protective long-term adaptative immunity to tumors. In vivo Winn tests performed in SCID mice showed that the expression of anti-CD16 scFv on tumor cells, but not of the negative control anti-phOx scFv, prevented tumor cell growth. Thus, expression of FcR antibodies or other FcR-specific ligands on tumor cells represents a novel and potent antibody-based gene therapy approach, which may have clinical applications in cancer
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Recombinantes de Fusão
/
Terapia Genética
/
Receptores do Fator de Crescimento Derivado de Plaquetas
/
Receptores de IgG
/
Carcinoma Pulmonar de Células não Pequenas
/
Neoplasias Pulmonares
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Gene Ther
Assunto da revista:
GENETICA MEDICA
/
TERAPEUTICA
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
França