Experimental therapy of allogeneic solid tumors induced in athymic mice with suicide gene-transducing replication-competent foamy virus vectors

Abstract

A replication competent foamy virus derived retroviral vector expressing suicide genes has been constructed and characterized in vitro. Here we used vectors expressing the purine nucleoside phosphorylase (FOV-7/pnp), the nitroreductase (FOV-7/ntr), or the thymidine kinase (FOV-7/tk) suicide gene in an in vivo athymic (nude) mice/human glioblastoma tumor model. Gliomas were induced by subcutanous injection of U87 tumor cells. The virus vector was injected when the tumor became visible. Mice with vector virus-injected tumors were treated with the respective prodrug. The treatment resulted in significant inhibition of tumor growth. Surprisingly, in mice with vector virus-injected tumors without prodrug treatment a similar suppression of tumor growth was observed. In 65% (pnp vector), 75% (ntr vector) and 37% (tk vector) of these mice the tumors stopped growing or vanished and the animals remained tumor free for the 25 weeks of the experiment, whereas all mice of the control groups had to be killed because of the tumor growth. In control experiments, the suppression of tumor growth could also be observed when wild-type foamy virus was injected instead of the suicide gene-transducing vectors. Similar results were obtained using the nude mice/G59 human glioblastoma tumor model. In conclusion, the experiments demonstrate an oncolytic activity of foamy virus replication in a nudemice glioblastoma xenograft tumor model. The analysis of vector virus DNA by PCR revealed that the vector persisted in different organs of the animals irrespective of the use of a prodrug or the elimination of a tumor. Cancer Gene Therapy (2005) 12, 947-953.

Foamy virus infection in primates

“…Heinkelein et al. [30] developed FV vectors to deliver suicide‐genes to solid tumors, using an athymic mouse model. Suicide‐gene therapy is a two‐step process that has been developed to target and eliminate solid tumors.…”

Adenovirus-mediated hypoxia-targeted gene therapy using HSV thymidine kinase and bacterial nitroreductase prodrug-activating genes in vitro and in vivo

“…Others found NTR/ CB1954 to suppress tumor growth more efficiently in vivo than HSVtk/GCV. 27 Both prodrug-activating systems demonstrate efficacy in a variety of models. However, the use of HSVtk/GCV in cancer gene therapy may be limited owing to the requirement of target cell division, as HSVtk/GCV is only active in dividing cells.…”

Cremophor-free intravenous self-microemulsions for teniposide: Safety, antitumor activity in vitro and in vivo

“…Male BALB/c mice (6-8 weeks) were inoculated subcutaneously with 0.2 mL of U87MG cells (1×10 7 /mL) at the right armpit to obtain glioma models (Heinkelein, Hoffmann et al 2005). 4 weeks later, the U87MG tumor-bearing mice were randomly divided into three groups (6 for 5 % glucose as control, 6 for VUMON, and 6 for TEN-SMEDDS).…”