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Kudo-Saito C Garnett CT Wansley EK Schlom J Hodge JW 《Cancer immunology, immunotherapy : CII》2007,56(12):1897-1910
Systemic IL-2 is currently employed in the therapy of several tumor types, but at the price of often severe toxicities. Local
vector mediated delivery of IL-2 at the tumor site may enhance local effector cell activity while reducing toxicity. To examine
this, a model using CEA-transgenic mice bearing established CEA expressing tumors was employed. The vaccine regimen was a
s.c. prime vaccination with recombinant vaccinia (rV) expressing transgenes for CEA and a triad of costimulatory molecules
(TRICOM) followed by i.t. boosting with rF-CEA/TRICOM. The addition of intratumoral (i.t.) delivery of IL-2 via a recombinant
fowlpox (rF) IL-2 vector greatly enhanced anti-tumor activity of a recombinant vaccine, resulting in complete tumor regression
in 70–80% of mice. The anti-tumor activity was shown to be dependent on CD8+ cells and NK1.1+. Cellular immune assays revealed that the addition of rF-IL-2 to the vaccination therapy enhanced CEA-specific tetramer+ cell numbers, cytokine release and CTL lysis of CEA+ targets. Moreover, tumor-bearing mice vaccinated with the CEA/TRICOM displayed an antigen cascade, i.e., CD8+ T cell responses to two other antigens expressed on the tumor and not the vaccine: wild-type p53 and endogenous retroviral
antigen gp70. Mice receiving rF-IL-2 during vaccination demonstrated higher avidity CEA-specific, as well as higher avidity
gp70-specific, CD8+ T cells when compared with mice vaccinated without rF-IL-2. These studies demonstrate for the first time that the level and
avidity of antigen specific CTL, as well as the therapeutic outcome can be improved with the use of i.t. rF-IL-2 with vaccine
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