TGF-beta for Pleurodesis

DESCRIPTION (provided by applicant): Approximately 50,000 cancer patients a year have recurrent fluid accumulation in the space between their chest wall and lung. This condition is called malignant pleural effusion (MPE). This fluid impairs breathing and worsens the quality of life in these patients. The current treatments are not ideal and include removing the fluid by repetitive needle aspiration, discontinuous aspiration via pleural catheter, and elimination of the space between the chest wall and lung by scarification, a process known as pleurodesis. Pleurodesis is often the treatment of choice in these cases. Creating a wound-healing environment in the pleural space therapeutically produces a pleurodesis. This can be done by physical abrasion of the visceral and parietal pleura, by instilling an irritant, or by creating a chemical burn on the pleural surfaces. All of these treatment options possess significant limitations. Abrasion requires hospitalization and general anesthesia, the most common irritant used is talc, which has occasional fatal side effects, and the induction of a pleural burn can be extremely painful. All of these treatments are employed to try to induce a collagenous scar to form between the parietal and visceral pleura. Transforming Growth Factor beta (TGF-beta) has been used to accelerate wound healing in several models. Additionally, TGF-beta is known to induce collagen formation. Our group has shown that a single injection of TGF-beta into the pleural space is sufficient to create an excellent pleurodesis in several animal models. The pleurodesis elicited via TGF-beta does not induce the same inflammatory mediators as talc and tetracycline derivatives in these models suggesting that fewer acute side effects may accompany pleurodesis created with TGF-beta. We hypothesize that TGF-beta will induce an effective pleurodesis in patients with MPE. In the current proposal we will apply our knowledge of TGF-beta induced pleurodesis in animal models to human patients with MPE. We will confirm that TGF-beta can produce a pleurodesis in this population. We will also assess the acute side effects of TGF-beta pleurodesis. Finally, we will monitor the patient to confirm that once a pleurodesis is obtained with TGF-beta it is irreversible and persistent. The successful conclusion of this proof of concept study will provide sufficient data to move forward toward the commercialization of TGF-beta for this indication.