Antitransforming growth factor-β antibody 1D11 ameliorates normal tissue damage caused by high-dose radiation

Purpose The aim of this study was to determine whether a neutralizing transforming growth factor-β (TGFβ) antibody can prevent radiation (RT) induced lung injury. Methods and Materials Fractionated and sham right lung irradiation in Fischer 344 rats was delivered to assess the radioprotective effect of the antibodies. Animals were divided into the following groups: (1) control (sham RT, control antibody 13C4); (2) RT (800cGy x 5)+13C4); (3) RT + 0.1 mg/kg 1D11 anti-TGFβ antibody; and (4) RT + 1 mg/kg 1D11 antibody. Antibodies were intraperitoneally administered immediately after the last fraction of RT. Animals were sacrificed at 6 and 26 weeks after irradiation. Lungs were assessed for histologic changes, activation of macrophages, expression/activation of TGFβ and its signal transduction pathway. Results At 6 weeks post-RT, there was a significant reduction in macrophage accumulation (p = 0.041), alveolar wall thickness (p = 0.0003), and TGF-β activation (p = 0.032) in animals receiving 1.0 mg/kg 1D11 vs. in the control group. However, at 6 weeks, the low dose of 1D11 antibody (0.1 mg/kg) failed to produce any significant changes. At 6 months post-RT, radioprotection is apparent for the group receiving 1.0 mg/kg 1D11, with activated macrophages (p = 0.037), alveolar wall thickness (p = 0.0002), TGFβ activation (p = 0.002) and its signal transduction proteins (p < 0.05) compared with the control group. Conclusions Administration of a single dose of 1.0 mg/kg of the anti-TGFβ antibody 1D11 resulted in decreased morphologic changes, inflammatory response, and reduced expression and activation of TGFβ 6 weeks and 6 months after 40 Gy to the right hemithorax. Targeting the TGFβ pathway may be a useful strategy to prevent radiation-induced lung injury