PURPOSE We investigated whether an armed viral platform, where lytic property of a viral infection is coupled to viral-mediated delivery of therapeutic genes, could increase the therapeutic potential of a viral-based therapy. EXPERIMENTAL DESIGN We generated interleukin (IL)-12-expressing oncolytic adenovirus (YKL-IL-12) and IL-12- and B7-1-expressing (YKL-IL12/B7) oncolytic adenovirus. Thera...

The objective of the research was to investigate serum levels of interleukin-12 (IL12) in relation to percentage of yeast-like fungi colonies residing in the gastrointestinal tract in children and adolescents with type 1 diabetes mellitus (T1DM). The study involved 83 children and adolescents, including 53 T1DM patients and 30 healthy control subjects. In the studied population biochemical test...

OBJECTIVE To assess the effectiveness of in vivo gene therapy to treat subcutaneous tumors generated from murine lung cancer cells. MATERIAL AND METHODS C57BL/6 mice received subcutaneus injections of 5 x 105 cells from the murine Lewis lung cancer cell line. By 10 days, subcutaneous tumors of approximately 5 mm diameter were formed. At that point, treatment was provided by intratumor injecti...

PURPOSE The adoptive cell transfer (ACT) of CD8(+) T cells is a promising treatment for advanced malignancies. Lymphodepletion before ACT enhances IFNγ(+)CD8(+) T cell (Tc0)-mediated tumor regression. Yet, how lymphodepletion regulates the function and antitumor activity of IL17A(+)CD8(+) T cells (Tc17) is unknown. EXPERIMENTAL DESIGN To address this question, pmel-1 CD8(+) T cells were polar...

Tumor microenvironment is extremely immunosuppressive, preventing efficient induction of antitumor immunity. To overcome tumor-mediated immunosuppression and enhance the potency of immunogene therapy, oncolytic adenovirus (Ad) co-expressing interleukin (IL)-12 and vascular endothelial growth factor (VEGF)-specific short hairpin ribonucleic acid (shVEGF; RdB/IL12/shVEGF) was generated. Intratumo...

Host responses are increasingly considered important for the efficacious response to experimental cancer therapies that employ viral vectors, but little is known about the specific nature of host responses required. In this study, we investigated the role of host type I interferons (IFN-I) in the efficacy of virally delivered therapeutic genes. Specifically, we used a Semliki Forest virus encod...

Purpose: Interleukin-12 (IL12) is a potent proinflammatory cytokine with antitumor activity. Its heterodimeric nature makes it compatible with a large variety of different immunocytokine formats. Here we report the design, production, and characterization of a novel immunocytokine, based on the fusion of the F8 antibody (specific to the alternatively spliced EDA domain of fibronectin, a marker ...

Host responses are increasingly considered important for the efficacious response to experimental cancer therapies that employ viral vectors, but little is known about the specific nature of host responses required. In this study, we investigated the role of host type I interferons (IFN-I) in the efficacy of virally delivered therapeutic genes. Specifically, we used a Semliki Forest virus encod...

Purpose: The adoptive cell transfer (ACT) of CD8þ T cells is a promising treatment for advanced malignancies. Lymphodepletion before ACT enhances IFNgþCD8þ T cell (Tc0)–mediated tumor regression. Yet, how lymphodepletion regulates the function and antitumor activity of IL17AþCD8þ T cells (Tc17) is unknown. Experimental Design: To address this question, pmel-1 CD8þ T cells were polarized to secr...

PURPOSE Interleukin-12 (IL12) is a potent proinflammatory cytokine with antitumor activity. Its heterodimeric nature makes it compatible with a large variety of different immunocytokine formats. Here we report the design, production, and characterization of a novel immunocytokine, based on the fusion of the F8 antibody (specific to the alternatively spliced EDA domain of fibronectin, a marker o...