Article Abstract

Efficient cancer gene therapy with a Del1 fragment administered by hypodermic injection in a mouse explanted tumor model

Authors: Hisataka Kitano, Tomomi Ishikawa, Eri Tamura, Shinichiro Kokubun, Chiaki Hidai


Background: Cancer gene therapy using non-viral vectors has potential therapeutic value because it can be used repeatedly for long periods with safety and low costs. It has been reported that gene therapy with an E3C1 fragment of Del1 in a mouse explanted tumor model shows long-term effects when intratumorally injected in the form of DNA. The present study examined whether this therapy is effective when injected hypodermically.
Methods: Mice with explanted tumors of A431 human squamous carcinoma cells were treated with a non-viral plasmid vector encoding E3C1. The plasmid was injected subcutaneously every week. Evaluation of lifespan and histochemical analyses were then performed.
Results: After 2 weeks of treatment, tumor volumes of control and treated mice were 4,988±1,477 and 1,443±1,523 mm3, respectively (control vs. E3C1, P<0.05). Control mice died or were euthanized within 32 days. In contrast, E3C1-treated mice started to die at day 39, and two of six mice survived for 60 days at which time the mice were euthanized (P<0.05). Histochemical analyses showed enhanced apoptosis in tumors, but not in other organs or injection sites of E3C1-treated mice.
Conclusions: Cancer gene therapy with a non-viral vector encoding the E3C1 fragment resulted in significant improvement of lifespan when administered by hypodermic injection.