Rapidly boosting innate immunity in the lungs to protect against pneumonia

描述（由申请人提供）：问题：肺炎是全球死亡的主要原因。即使在发达国家，它仍然是感染死亡的主要原因，也是治疗其他疾病的病人的严重并发症。当宿主耐药性水平下降（例如免疫功能低下的癌症患者）和病原体暴露水平增加（例如大流行、生物恐怖和生物战）时，肺部感染的威胁就会升高。急性白血病患者是目前最危险的患者之一，因为他们面临着因癌症治疗而导致的严重免疫功能低下。很多时候，这些风险阻碍了完整的癌症治疗计划的完成。因此，每年估计有44,700名白血病患者花费超过15亿美元用于预防肺炎的一系列治疗。

DESCRIPTION (provided by applicant): Problem: Pneumonia is the leading cause of death worldwide. Even in developed countries, it continues to be the leading cause of death from infection and a serious complication for patients being treated for other diseases. The threat of lung infections is elevated when there is a decreased level of host resistance (e.g. immunocompromised cancer patients) and when there is an increased level of pathogen exposure (e.g. pandemics, bioterror, and biowarfare). Acute leukemia patients are currently some of the most at-risk patients, as they are faced with significant immunocompromise resulting from their cancer treatments. Many times these risks prevent the full cancer treatment plan from being completed. As a result, each year an estimated 44,700 leukemia patients spend more than one-half billion dollars on a range of treatments in an effort to prevent pneumonia. Pulmotect's Solution: Pulmotect has identified and is developing a novel technology to address the risks of inhaled microbes. Our therapeutic (PUL-042) is a combination of two TLR ligands that stimulate the lung's own innate defense mechanisms to create a hostile environment for pathogens and reduce or prevent infection. Both in vitro and in vivo experiments have been completed to validate this technology. Importantly, because of the low cell-turnover rate, the lung epithelium is resistant to chemotherapy drugs so the innate immune response remains intact. It is in these most at-risk patients where proof-of-concept can be captured for additional markets. The focus of this proposal is to accomplish key milestones that will validate this technology for commercialization. This SBIR application is focused on addressing important preclinical important issues. The three Aims included are designed to validate and expand upon the proof-of-concept data already obtained. The Aims are focused for transitioning this technology into the clinic. Achieving these milestones would provide significant data for an IND application for a product that is safe and efficacious. Positive results from this phase I proposal would potentially lead to a phase II SBIR application to perform an in-depth study of the therapy in a second animal model, including FDA approved safety and toxicity studies. Additionally, by demonstrating subsequent discoveries in Pulmotect's pipeline, additional outside funds from investors can better be pursued to transition this technology into the clinic and market place. Overall, the outlined milestones of this proposal would build upon previous work, add to the foundation of this platform technology, and help bring this technology to the clinic. ) PUBLIC HEALTH RELEVANCE: Pulmotect, Inc is developing novel therapeutics that stimulates the innate immune system to protect against infectious diseases, even in cases of severely compromised immunity. Proof-of-concept data has shown that this technology effectively protects against a broad range of inhaled pathogens. This project will provide significant data to help transition this technology from the lab to the clinic, where physicians are asking to use the technology to benefit their patients.