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Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 156.98K | Year: 2014

DESCRIPTION (provided by applicant): This SBIR project is focused to develop, validate and commercialize an advanced high-throughput anti- tumor drug screening platform (HTS) which employs a new 3D HuBioGEM assay technology. Preclinical drug screening is commonly performed using biochemical and cell-based assay systems. In recent years, more relevant 3D spheroid models have been developed using microcarrier, pHEMA- coating, gel-layer and hanging-drop techniques. Although useful, these require difficult culture protocols, provide undesirable endpoints and/or are not efficient for automated applications. We have created a novel HuBioGEM culture system by formulating patented HuBiogel (human biomatrix) with unique paramagnetic particles (GEM). Employing 3D magnetic-biogel and 384-array culture strategies, we propose to develop a robust human microtumor assay platform for drug efficacy profiling. Phase I technical goals are: i) Establish 3D tumor production, culture and analysis protocols using HuBioGEM, NCI


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 171.65K | Year: 2009

DESCRIPTION (provided by applicant): Over 30,000 Americans die each year from prostate cancer, making it the second most lethal form of cancer affecting men in the U.S. Many of these deaths could be prevented if the cancers were detected before the tumor escaped the prostate. Our goal for this research project is to develop a simple blood test that will dramatically improve a physician's ability to judge whether an abnormal PSA level is due to a metastatic prostate tumor or to a benign prostatic condition. The availability of this assay will eliminate thousands of unnecessary prostate biopsies with their inherent pain, undesirable side effects, and cost. In addition, the Vivo assay should make it possible to detect a large portion of the 15-20% of existing prostate tumors that are missed by the PSA test. Vivo's research plan is designed to identify tumor-associated autoantibodies which may be present at low levels in normal serum but increase during the early stages of prostate cancer. Our approach is particularly novel in that it focuses on autoantibodies of the IgM and IgA isotypes which are generally ignored in traditional epitope discovery strategies. Our approach also bypasses the common practice of pre-subtracting the phage library against Igs from normal sera; while the subtractive step may speed up the overall biopanning process, it also interferes with the discovery of potentially important diagnostic antibodies which are already present at low levels in normal sera but are elevated as the cancer progresses. We propose to achieve two specific aims: 1. To identify a group of peptides that are recognized by either IgM or IgA autoantibodies in sera from patients with aggressive prostate cancer; and 2. To compare the reactivities of these peptides with individual patient sera (aggressive and indolent cancers; BPH) and with healthy controls. To achieve these goals, we will prepare several thousand individually-amplified peptide phage clones and will use high throughput techniques to measure their reactivities with multiple serum samples. The new assay will provide significant improvements in the specificity and sensitivity of prostate cancer diagnostics, and this should lead to wider acceptance of screening programs for the early detection of prostate cancer and to significant declines in the prostate cancer death rate. PUBLIC HEALTH RELEVANCE: The goal of this research project is to develop a new blood test for the early diagnosis of prostate cancer which will make the current PSA test more sensitive and more reliable. This will encourage more physicians to support annual screening of their patients at risk for this cancer and will thus lead to decreases in the death rate due to this disease.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 700.37K | Year: 2006

DESCRIPTION (provided by applicant): In our initial R&D effort we successfully demonstrated the feasibility of a novel human biomatrix system (HuBiogel) in designing 3D bioassay system for in vitro examination of tumorigenesis process. The overall goal was and is to develop and commercialize these human bioassay systems. Phase I work definitely established that new assay models exhibit many advantages over conventional monolayer cell cultures and animal-derived biomatrix systems. HuBiogel assays of defined bioactivity or environment are established for real-time analysis of tumor growth and angiogenesis. Based on project's clinical relevance, we also initiated active collaborations with two renowned cancer researchers. With this promising technology, we propose three extended tasks to fully accomplish our R&D goals. They are: 1) Establish efficient protocols for biomatrix production, analysis and formulation at commercial scale using automated technologies; 2) Complete the development of 3D tumor growth, invasion and angiogenesis assay platform using human breast and brain tumor cell models; 3) Validate functional properties of HuBiogel assays by established cellular and molecular analysis techniques. Our integrated technology will allow precise real-time analysis of tumorigenesis cascade. New 3D assay technology will provide more clinical relevance as it emulates human tumor-like biology and function. This advanced bioassay system will be useful for endpoint analysis of early to late tumorigenesis stages, parallel evaluation of specific positive and negative regulators and phenotypic profiling of tumor cells or biopsies. Thus, the timely completion of this promising R&D project will positively impact cancer biology, drug discovery and therapeutic research markets. Project Relevance: No acceptable commercial tumor assay model currently exists which utilizes a natural or defined human biomatrix system. VBI will develop reusable and disposable 3D tumor growth, invasion and angiogenesis assay platforms. Sale of HuBiogel, pre-packed assay kits and in-house drug testing services would have a significant world-wide market in basic, biomedical and cancer research fields.


Grant
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 269.60K | Year: 2006

DESCRIPTION (provided by applicant): Apoptosis is well recognized as an important biological process that controls cancer development and progression and the efficacy of chemotherapeutic drugs depends largely on their ability to induce apoptosis. Modern biology has suggested that cancer drug discovery based on molecular differences between tumor and normal cells is a feasible approach. Bcl-2, a critical anti-apoptotic protein, is overexpressed in the majority of malignancies and contributes to cancer development and drug resistance. Agents that target Bcl-2, therefore, offer a therapeutic advantage. Recently, we discovered a novel Nur77-Bcl-2 apoptotic pathway in cancer cells, in which orphan nuclear receptor Nur77 (also known as TR3) migrates from the nucleus to mitochondria where it interacts with Bcl-2 to induce cytochrome c release, which triggers apoptosis. Importantly, the interaction of Nur77 with Bcl-2 converts Bcl-2 from protector to killer, offering an opportunity to develop more effective anti- cancer agents. We hypothesize that peptides derived from the Bcl-2-binding region in Nur77 protein can be developed as therapeutic agents targeting Bcl-2-expressing cancer cells. In our preliminary studies, we found that a cell-permeable peptide with 9 amino acid residues from the Nur77 protein effectively induces apoptosis of cancer cells in vitro and in animals. The peptide, like Nur77, targets mitochondria through its interaction with Bcl-2 and induces Bcl-2 conformational change. In this STTR Phase I application, we propose to improve the pharmacological and biopharmaceutical properties by modifying the lead Nur77 peptide. Our goal will be accomplished by three aims: (1). Design and synthesis of Nur77 peptides using amino acid substitution and conjugation with a tumor selective homing peptide; (2). Evaluate Nur77 peptides for their mitochondrial targeting, Bcl-2 interaction, conformational change, and apoptosis induction; (3). Evaluate Nur77 peptides for their pharmacokinetics, tolerability in mice and in vivo efficacy. Our goal is to identify a stable, tumor-selective, cell-permeable peptide with minimal toxicity and suitable pharmacokinetics for Phase II development and commercialization.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 219.81K | Year: 2015

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