Asbestos Research Today is a free monthly online journal that collates and summarizes the latest research about Asbestos, including details on mesothelioma, lung disease, dangers, effects, risks. | ||||||||
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Antitumor activity of the intratumoral injection of fowlpox vectors expressing a triad of costimulatory molecules and granulocyte/macrophage colony stimulating factor in mesothelioma.Triozzi PL, Aldrich W, Allen KO, Lima J, Shaw DR, Strong TV University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL 35294-3300, USA. pierre.triozzi@ccc.uab.edu Deficiency in costimulatory molecule expression has been implicated in the ability of tumors to escape immune effectors. The activity of the intratumoral administration of recombinant fowlpox vectors expressing a triad of costimulatory molecules (rF-TRICOM) was evaluated in the asbestos-induced AB12 and AC29 mouse models of mesothelioma. Mesothelioma cell infected with rF-TRICOM expressed high levels of the costimulatory molecules. Prolongation of survival was observed in mice receiving rF-TRICOM in AB12 and AC29 intraperitoneal models. Complete tumor regressions were observed in mice receiving intratumoral rF-TRICOM in the AB12 subcutaneous tumor model. Tumor regressions were associated with the development of serum IgG reactivities to mesothelioma-associated determinants and specific systemic cytolytic activity, and responding mice were capable of rejecting tumors upon re-challenge. Antitumor activity was also observed in mice with established AB12 tumor vaccinated with irradiated rF-TRICOM-infected AB12 cells. The antitumor activity of intratumoral rF-TRICOM was superior to that of the intratumoral injection of a fowlpox vector expressing granulocyte-macrophage colony stimulating factor (rF-GM-CSF). AB12 and AC29 tumors were found to produce GM-CSF and to have substantial macrophage infiltration. Production of GM-CSF decreased in vivo in tumors injected with rF-TRICOM. rF-TRICOM and wild-type fowlpox inhibited the growth of AB12 and AC29 cells in vitro; less inhibition was observed with rF-GM-CSF. These results indicate that the intratumoral injection of rF-TRICOM has significant activity in mouse models of mesothelioma and can elicit a systemic antitumor immune response. The results also suggest potential limitations to the intratumoral administration of cytokines, such as GM-CSF, in mesothelioma. Published 26 November 2004 in Int J Cancer, 113(3): 406-14.
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