PARENT SESSION
1:30 PM to 3:30 PM
Tuesday, April 23, 2002
Poster Session 16 Gene Therapy
Room: Nevada Exhibition Center

(P21-228) Soluble TGF- type II receptor gene therapy ameliorates acute radiation-induced pulmonary injury in rats.

Rabbani, Zahid^*,1, Anscher, Mitchell¹, Zhang, Xiuwu¹, Samulski, Thaddeus¹, Li, Chuan-Yuan¹, Vujaskovic, Zeljko¹, ¹ Department of Radiation Oncology, Durham, NC

ABSTRACT-
TGF-1 has been implicated as a key cytokine in the development of radiation-induced lung injury. In its biologically active form, TGF1 binds to the TGF1 type II transmembrane receptor as the first step leading to activation of its signal transduction pathway. The objective of this study was to determine whether i.v. administration of recombinant human adenoviral vector which carries soluble TGF-1 type II receptor (TR-II) gene might reduce the availability of active TGF1 and thereby protect lung from radiation damage. Female Fisher 344 rats were randomized into four groups to receive: 1) Adenoviral vector (AdGFP) alone, 2) 30 Gy single dose of right hemithoracic radiation (RT) + treatment vector with TR-II gene (AdTR-II); 3) RT alone; 4) Control. In the RT + AdTR-II group, there was a significant reduction in respiratory rate (p = 0.002) at four weeks after treatment as compared to RT alone group. In addition, there was a significant reduction in both lung structural damage and in macrophage number (p= 0.02) in animals receiving gene therapy after radiation. The tissue protein expression of active TGF- was significantly reduced in rats after RT + AdTR-II treatment. This preliminary results show the ability of adenovirus mediated soluble TR-II gene therapy to reduce tissue level of active TGF- and consequently ameliorate radiation-induced lung injury in rats 4 weeks after irradiation. Future studies are needed to confirm these results after longer follow up.

KEYWORDS: Gene therapy, Radiation, TGF-, Pulmonary toxicity