LXS, LLC — Department of Health and Human Services SBIR Phase I: 300

Description

Over a quarter century of research has significantly improved our understanding of the circulating cardiovascular system and its cellular components However study of the parallel lymphatic system has lagged far behind limiting our understanding of this complex and potentially clinical beneficial network The lymphatic system is comprised of an extensive network of vessels and nodes that parallel the venous vasculature Peripheral lymphatic channels combine to form a single thoracic duct that enters the venous system at the confluence of the left internal jugular and subclavian veins It is known that the lymphatic system plays a number of roles in GI physiology including fluid homeostasis digestion and cell mediated immunity More recent research suggests potentially critical roles in pathophysiological conditions such as diabetes cancer cirrhosis and autoimmune disorders A significant obstacle in advancing lymphatic research is the ability to safely and easily collect circulating lymph and its cellular components The majority of studies on circulating lymphatic cells depend on cells collected from peripheral blood where lymphocytes make up less than of circulating cells Peripheral blood collection techniques the predominant type is leukapheresis are time consuming and expensive Processing can damage cells altering their genetic profile and impacting behavior Because of the complexity and time required it is difficult to obtain multiple scheduled samples and truly map changes in lymphocyte populations and non cellular components in real time Direct sampling from the lymphatic system requires a complex open surgical cut down to locate and cannulate the thoracic duct which is not feasible for widespread clinical use particularly in a research setting We are proposing a novel sampling method to access and aspirate lymphocytes fluid and non cellular components directly from the thoracic duct Our approach involves a novel access catheter placed via the central venous system under ultrasound visualization Catheterization is safe and predictable leveraging existing central venous access and guidewire techniques Access would provide an exponentially higher concentration of desirable cell types This SBIR Phase I project consists of two Specific Aims designed to advance our technology through proof of concept design testing and fabrication and pilot production Successful completion of these Aims will place the company in a position to conduct a first in human sampling study as part of Phase II A safe and effective method to collect large quantities of circulating lymphocytes would be of benefit in advancing basic and translational research in gastrointestinal medicine catalyzing development of new clinical applications in infectious disease oncology and fluid management Once fully realized this method provides an opportunity to launch a wide range of classification studies to better understand circulating lymphatic cell characteristics and dynamics Downstream clinical applications may include selective removal of specific T cell phenotypes in GI autoimmune conditions large volume cell collection for ex vivo manipulation ex CAR T cell therapy dendritic vaccine development and removal manipulation of non cell components like exosomes cholesterol cylomicons or interstitial fluid Over a quarter century of research has significantly improved our understanding of the circulating cardiovascular system and its cellular components However study of the parallel lymphatic system has lagged far behind limiting our understanding of this complex and potentially clinical beneficial network While it is known that the lymphatic system plays a number of roles in GI physiology and pathophysiology a significant remaining obstacle is the ability to safely and easily collect circulating lymph and its cellular components We are proposing a novel transvascular access device to safely and repeatedly cannulate the thoracic duct A safe and effective method to access the lymphatic system directly would be of benefit in advancing basic and translational research in gastrointestinal medicine catalyzing development of new clinical applications in infectious disease oncology and fluid management Once fully realized this method provides an opportunity to launch a wide range of classification studies to better understand circulating lymphatic cell characteristics and dynamics Downstream clinical applications may include selective removal of specific T cell phenotypes in GI autoimmune conditions large volume cell collection for ex vivo manipulation and manipulation of non cell components like exosomes cholesterol cylomicons or interstitial fluid