Anti-4-1BB scFv immunogene therapy and low dose cyclophosphamide exhibit a synergistic antitumor effect in established murine lung tumors.
Cancer Biol Ther
; 8(8): 707-13, 2009 Apr.
Article
em En
| MEDLINE
| ID: mdl-19417562
ABSTRACT
T-cell costimulatory molecules such as 4-1BB may provide a distinct and important signal for promoting positive immune regulation. 4-1BB is thought to have potential use as a cancer immunotherapeutic drug. In our previous study, a nonreplicative adenovirus (Ad.4-1BB scFv) carrying single-chain Fv fragments (scFv) specific for the 4-1BB gene (anti-4-1BB scFv) possessed remarkable in vivo anti-hepatoma efficacy. However, monotherapy achieved by triggering 4-1BB signaling was not sufficient to induce eradicative antitumor activities in low immunogenic tumors. It is of great interest to explore any possible synergistic antitumor effect of 4-1BB signaling combined with low dose cyclophosphamide (CTX), which is well documented to inhibit the suppressive capability of regulatory T-cells in mice and humans. In the present study, recombinant nonreplicative adenoviruses carrying an anti-4-1BB scFv gene were generated, characterized and explored for their stimulation of antilung tumor (TC-1) immunity in immunocompetent C57BL/6 mice. Compared to adenovirus and cyclophosphamide alone, adenovirus-mediated anti-4-1BB scFv in combination with low dose CTX treatment could obviously augment the antitumor activity, in which some established TC-1 tumors were eradicated and the survival of mice was significantly extended. This synergistic antitumor effect could be largely attributed to the depletion of T regulatory cells induced by low dose CTX. These findings may provide a new and promising strategy for immunogene therapy against cancer.
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Base de dados:
MEDLINE
Assunto principal:
Região Variável de Imunoglobulina
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Terapia Genética
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Antineoplásicos Alquilantes
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Ciclofosfamida
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Ligante 4-1BB
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Neoplasias Pulmonares
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article