SBIR-STTR Award

In-Situ Gelling Protein Polymer Intravascular Embolic Agent for Hepatic Carcinoma
Award last edited on: 1/18/2018

Sponsored Program
STTR
Awarding Agency
NIH : NCI
Total Award Amount
$1,594,378
Award Phase
2
Solicitation Topic Code
102
Principal Investigator
Hamid Ghandehari

Company Information

TheraTarget Inc

36 South Wasatch Drive
Salt Lake City, UT 84112
   (801) 587-1514
   darwin.cheney@utah.edu
   www.theratarget.com

Research Institution

University of Utah

Phase I

Contract Number: 1R41CA168123-01
Start Date: 9/21/2012    Completed: 8/31/2013
Phase I year
2012
Phase I Amount
$100,000
This Phase I proposal addresses the significant need for improved treatment options for patients with liver cancer, the fifth highest incidence of cance in the world. Because of the lack of symptoms, hepatocellular carcinoma (HCC) is detected at advanced stages in 84% of cases, for which the 1-year survival rate is 22% and at 5 years it is 5%. The only curative option for advanced HCC is surgical liver resection and liver transplantation, unfortunately not available to most patients due to the lack of donor livers and the rapid progression of the disease. As HCC is generally unresponsive to systemic chemotherapy, transcatheter arterial chemoemobolization (TACE) is the most widely used, localized treatment that can slow the progression of the disease. Current embolizing agents are deficient in precision of catheter delivery or compatibility for effective delivery of chemotherapeutic agents, especially high-molecular weight biotherapeutics. The objective of the proposed work is to develop a novel liquid embolizing agent composed of the genetically engineered protein polymer, SELP (silk- elastinlike protein), which based on our previous work has demonstrated properties uniquely suited for this application. Unlike existing agents, the SELP embolizing agent would be injectable as a liquid, able to penetrate into the tumor arteries, and transform to an insoluble hydrogel in-situ forming a substantially durable occlusion. The embolizing liquid would be completely aqueous and compatible with drugs and new biotherapeutics, enabling their localized controlled release. The protein-based SELP would eventually biodegrade, enabling subsequent TACE treatments. If successful, SELP liquid embolic would enable the controlled delivery of chemotherapeutic drugs and new biotherapeutic agents with increased precision of transcatheter delivery for more selective embolization, reduced off-target toxicity, and reduced collateral damage to the healthy liver. Consequently, TACE treatment could be offered to a larger patient population with greater number of tumors and/or greater tumor size. The aims of the research are: (1) to develop SELP liquid embolic injection solution formulations; (2) to determine the gelation rate and gel strength of SELP fluids at their maximum injectable viscosity; (3) to assess their occlusion of simulated arterial channels in-vitro using a microfluidic device; and (4) evaluate the performance of SELP fluids in transcatheter arterial embolization in-vivo in the liver.

Public Health Relevance:
This Phase I proposal details the rationale and the research plan for the development of a novel liquid embolizing agent composed of the genetically engineered protein polymer, SELP (silk- elastinlike protein), for treatment of unresectable hepatocellular carcinoma by transcatheter arterial chemoembolization (TACE). The SELP embolic would improve the precision of embolization, the compatibility with newly developed drugs, and the selectivity of tumor-specific therapy. Consequently, TACE treatment could be offered to a larger patient population with greater number of tumors and/or greater tumor size, for which few treatment options exist.

Public Health Relevance Statement:
This Phase I proposal details the rationale and the research plan for the development of a novel liquid embolizing agent composed of the genetically engineered protein polymer, SELP (silk- elastinlike protein), for treatment of unresectable hepatocellular carcinoma by transcatheter arterial chemoembolization (TACE). The SELP embolic would improve the precision of embolization, the compatibility with newly developed drugs, and the selectivity of tumor-specific therapy. Consequently, TACE treatment could be offered to a larger patient population with greater number of tumors and/or greater tumor size, for which few treatment options exist.

NIH Spending Category:
Bioengineering; Biotechnology; Cancer; Digestive Diseases; Liver Cancer; Liver Disease; Orphan Drug; Rare Diseases

Project Terms:
Address; Amino Acid Sequence; Antineoplastic Agents; aqueous; Arterial Embolization; Arteries; artery occlusion; base; Biocompatible Materials; Biological; Biological Products; Biological Response Modifier Therapy; Blood capillaries; Blood Circulation; Blood flow; Caliber; cancer therapy; capillary; Carcinoma; Catheters; Chemicals; Chemoembolization; chemotherapeutic agent; chemotherapy; controlled release; Development Plans; Dimethyl Sulfoxide; Disease Progression; DNA biosynthesis; Drug Formulations; Effectiveness; Embolism; Engineering; Excision; Gel; Gene Delivery; Genes; Head and Neck Squamous Cell Carcinoma; Hepatic; Hydrogels; Image; Implant; improved; In Situ; In Vitro; in vivo; Incidence; Injectable; Injection of therapeutic agent; Learning; Length; Liquid substance; Liver; liver transplantation; Malignant neoplasm of liver; Mediating; Microfluidic Microchips; Microfluidics; Modeling; Molecular Weight; Nature; Necrosis; novel; Oils; Operative Surgical Procedures; Oryctolagus cuniculus; Palliative Care; particle; Particulate; patient population; Patients; Performance; Pharmaceutical Preparations; Phase; Polymers; prevent; Primary carcinoma of the liver cells; Property; Protein Engineering; Proteins; Radiation therapy; Recombinant DNA; Relative (related person); Research; response; Silk; Simulate; Solid; Solid Neoplasm; Solutions; Specific qualifier value; Staging; Survival Rate; Suspension substance; Suspensions; Symptoms; System; Testing; Therapeutic; Therapeutic Agents; Therapeutic Embolization; Time; Tissues; Toxic effect; tumor; Unresectable; Venous; Viscosity; Work

Phase II

Contract Number: 2R42CA168123-02A1
Start Date: 00/00/00    Completed: 00/00/00
Phase II year
2016
(last award dollars: 2018)
Phase II Amount
$1,494,378

This STTR Phase II proposal addresses the significant need for improved treatment options for patients with liver cancer, the fifth highest incidence of cancer in the world. Because of the lack of symptoms, hepatocellular carcinoma (HCC) is detected at advanced stages in 84% of cases, for which the 1-year survival rate is 22% and at 5 years it is 5%. The only curative option for advanced HCC is surgical liver resection and liver transplantation, unfortunately not available to most patients due to the lack of donor livers and the rapid progression of the disease. As HCC is generally unresponsive to systemic chemotherapy, transcatheter arterial chemoemobolization (TACE) is the most widely used, localized treatment that can slow the progression of the disease. Current embolizing agents are deficient in precision of catheter delivery or compatibility for effective delivery of chemotherapeutic agents, especially high-molecular weight biotherapeutics. The objective of the proposed work is to characterize the novel liquid embolizing agent composed of the genetically engineered protein polymer, SELP (silk-elastinlike protein)-815K, which based on our previous work has demonstrated properties uniquely suited for this application. Unlike existing agents, SELP-815K will be injectable as a liquid, able to penetrate into the tumor arteries, and transform to an insoluble hydrogel in-situ forming a substantially durable occlusion. The embolizing liquid will be completely aqueous and compatible with drugs and new biotherapeutics, enabling their localized controlled release. The protein-based SELP-815K will eventually biodegrade, enabling subsequent TACE treatments. SELP-815K liquid embolic will enable the controlled delivery of chemotherapeutic drugs and new biotherapeutic agents with increased precision of transcatheter delivery for more selective embolization, reduced off-target toxicity, and reduced collateral damage to the healthy liver. Consequently, TACE treatment will be offered to a larger patient population having a greater number of tumors and/or greater tumor size. The aims of the research are: (1) to characterize the delivery of single and multiple drugs via the SELP-815K gel network; (2) to conduct in vivo studies in the McA-RH7777 HCC liver tumor rat model to evaluate therapeutic performance; (3) to conduct SELP-815K manufacturing and analytical methods development; and (4) to conduct GLP preclinical toxicology and performance testing of manufactured SELP-815K embolic.

Public Health Relevance Statement:
NARRATIVE This STTR Phase II proposal details the rationale and the research plan for the development of a novel liquid embolizing agent composed of the genetically engineered protein polymer, SELP (silk-elastinlike protein)-815K, for treatment of hepatocellular carcinoma by transcatheter arterial chemoembolization (TACE). SELP-815K embolic will improve the precision of embolization, the compatibility with newly developed drugs, and the selectivity of tumor-specific therapy. Consequently, TACE treatment will be offered to a larger patient population having a greater number of tumors and/or greater tumor size, for which few treatment options exist.

Project Terms:
Acute; Address; analytical method; Animals; aqueous; Arteries; base; BAY 54-9085; Biological Products; Biological Response Modifier Therapy; biomaterial compatibility; bioresorption; Blood; Blood flow; Blood Tests; Caliber; cancer cell; cancer imaging; Carcinoma; Catheterization; Catheters; Characteristics; Chemoembolization; chemotherapeutic agent; chemotherapy; Chronic; Clinical Treatment; Clinical Trials; Collection; comparative efficacy; controlled release; design; Development Plans; Disease; Disease Progression; Doxorubicin; Drug Delivery Systems; drug distribution; Drug Formulations; Drug Kinetics; Endotoxins; Ensure; Evaluation; Excision; Excretory function; Family suidae; Fermentation; Formulation; Gel; Genetic Engineering; Gold; Grant; Guidelines; Health; Hemolysis; Hepatic; Hepatic artery; Human; Hydrogels; immunoreactivity; Implant; implantable device; implantation; improved; In Situ; In Vitro; in vivo; Incidence; Injectable; Injection of therapeutic agent; Interventional radiology; Intramuscular; Killings; Laboratories; Laboratory Personnel; Laboratory Procedures; Liquid substance; Liver; liver function; Liver neoplasms; liver transplantation; Lung; Magnetic Resonance Imaging; Malignant neoplasm of liver; Malignant Neoplasms; meetings; Metabolism; method development; Methods; Microfluidic Microchips; Modeling; Molecular Weight; nanoparticulate; novel; novel therapeutics; Operative Surgical Procedures; Oryctolagus cuniculus; patient population; Patients; Performance; performance tests; Pharmaceutical Preparations; Phase; Polymers; pre-clinical; Preparation; Primary carcinoma of the liver cells; Procedures; Process; Production; Property; Proteins; Qualifying; Rattus; Reaction; Research; Safety; scale up; Silk; Small Business Technology Transfer Research; Solid; Source; Staging; standard care; standard of care; Sterilization; Structure; Survival Rate; Symptoms; Syringes; System; systemic toxicity; Techniques; Testing; Therapeutic; Therapeutic Embolization; Time; Tissues; Toxic effect; Toxicity Tests; Toxicology; Treatment Efficacy; tumor; tumor vascular supply; Urine; Venous system; Viscosity; Work