Latest technologies from Fred Hutchinson Cancer Research Center

Neutralizing monoclonal antibodies against the KSHV gH/gL protein

jbcho@fredhutch.org — Fri, 09 Jan 2026 16:16:46 GMT

Neutralizing Antibodies Against Kaposi’s Sarcoma-Associated Herpesvirus A set of human-derived neutralizing antibodies against KSHV derived from KSHV-infected donors.

Kaposi’s Sarcoma-Associated Herpesvirus (KSHV) is an oncogenic human gamma herpesvirus responsible for Kaposi’s sarcoma (KS) and several rare but severe lymphoproliferative disorders. Infection is typically lifelong and clinically silent in immunocompetent individuals but becomes pathogenic under immunosuppression. Currently, there are no approved antivirals or prophylactic antibodies...

Accurate Modeling of Clinical Trials to Guide Antiviral Development

jbcho@fredhutch.org — Tue, 22 Jul 2025 14:52:41 GMT

Accurate Modeling of Clinical Trials to Guide Antiviral Development A mathematical framework to optimize antiviral drug selection, dosing, and clinical trial design.

While notable for enormous successes, clinical development of antiviral therapies lacks efficiency. The most salient example is the discovery and deployment of safe and effective antiviral drugs for SARS-CoV-2 which took nearly two years versus the one-year for vaccines. The blockbuster drug Paxlovid demonstrated unprecedented success in trials, leading to a 90% reduction in hospitalization and de...

Defining pathogenic IL-17 and CSF-1 gene expression signatures in chronic graftversus-host disease

jbcho@fredhutch.org — Tue, 04 Feb 2025 13:52:46 GMT

Predictive Immune Signatures for Chronic Graft Versus Host Disease (cGVHD) Dysregulated immune signatures may be well-suited for their ability to predict the effectiveness of agents targeting IL-17 and CSF-1. Chronic Graft Versus Host Disease (cGVHD) is the leading cause of non-relapse late morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT), affecting 30-50% of survivors. While there are an increasing number of approved therapies that target specific dysregulated immune pathways (including IL-17 and CSF1), only a minority of patients respon...

The androgen receptor regulates a druggable translational regulon in advanced prostate cancer

jbcho@fredhutch.org — Wed, 28 Aug 2024 12:54:09 GMT

Therapeutic targets to treat Androgen Receptor Deficient and Low Prostate Cancers Methods to treat Androgen Receptor Deficient and Low Prostate Cancers by targeting 4EBP1 Prostate cancer is the second most common male cancer, affecting cells of the prostate glands. About 90% of these early stage prostate cancers are dependent on androgens for growth, so inhibitors of the androgen receptor (AR) are often used as a treatment. However, prolonged use of androgen deprivation therapy (ADP) transforms many hormone sensitive prostate cancers into lethal castration-resistant pr...

Targeted delivery into CD90+ cells

jbcho@fredhutch.org — Wed, 28 Aug 2024 11:19:26 GMT

Selection and Use of Hematopoietic Stem Cells for Cell Transplantation and Gene Therapy Approaches Defined population predicts and quantitatively correlates with in vivo engraftment and multilineage potential. Hematopoietic stem cells (HSC) are the preferred target population for ex vivo gene therapy with applications ranging from rare monogenetic diseases to HIV. Currently, HSCs are isolated by the marker CD34. However, use of this population has several limitations. Fred Hutch researchers have identified a unique combination of genetic ...

Human and Nonhuman Primate Hematopoietic Stem/Repopulating Cells and Methods for Enriching The Same

jbcho@fredhutch.org — Wed, 28 Aug 2024 02:10:12 GMT

TARGETING PRAC1 IN CASTRATION RESISTANT PROSTATE CANCER

jbcho@fredhutch.org — Fri, 05 Jul 2024 15:27:00 GMT

Therapeutic peptide and biomarkers for castration-resistant prostate cancer (CRPC) Synthetic peptide targeting PRAC1 has been developed for the treatment of CRPC. Prostate cancer is an androgen dependent tumor, and the androgen receptor (AR) drives numerous mechanisms involved in disease progression. The standard therapy for metastatic PC involves various pharmacological approaches that inhibit the AR signaling axis. Despite initial profound responses to androgen deprivation therapies, most patients progress to castration-resistant prostate cancer (CRPC). Highly potent ...

Widely encoded colorectal cancer-associated bacterial genes in human microbiomes

jbcho@fredhutch.org — Wed, 12 Jun 2024 18:13:34 GMT

Bacterial gene-associated methods and compositions for diagnosing and treating colorectal cancer The present disclosure provides compositions and non-invasive methods for diagnosing a subject at risk for developing, or having, or at risk for progressing on colorectal cancer (CRC) based on analysis of bacterial species in the gut microbiome of the subject. This helps determine the appropriate treatment or management plan for these patients. Colorectal cancer (CRC) is one of the most common cancers globally. While epidemiological and disease cohort studies implicate a link between ...

NKG2D-SCD-T-Engager

jbcho@fredhutch.org — Sun, 10 Mar 2024 16:57:02 GMT

Therapeutics targeting NKG2D ligands for elimination of cancer cells and senescent cells A novel fusion protein targeting NKG2D ligands for eradicating cancer and senescent cells. Natural killer group 2 member D ligands (NKG2DLs) are consistently upregulated in cancer cells, senescent cells, and cells undergoing genotoxic stress. Moreover, NKG2D ligands are mostly unexpressed on healthy cells. Drs. Tom Schmitt and Roland Strong at the Fred Hutchinson Cancer Center have developed a novel fusion protein targeting NKG2D ligands for eradicating cancer and senescent cells. T...

Method of adoptive T cell therapy utilizing notch signaling to enhance efficacy

jbcho@fredhutch.org — Sun, 10 Mar 2024 16:21:59 GMT

Notch Activation to Improve Persistence and Efficacy of T Cell Therapies Method of using Notch ligands during culturing to improve the persistence and efficacy of CAR T cell therapies. While CAR T-based cell therapies are promising, the persistence, proliferation, and efficacy of those engineered T cell therapies need to be improved. Additionally, less differentiated T cell subsets (Tscm, Tcm) have been shown to deliver better anti-tumor efficacy. Researchers at the Fred Hutchinson Cancer Center have developed a method of using Notch ligands during culturing to improve ...

CCNA1 TCRs

jbcho@fredhutch.org — Tue, 12 Dec 2023 17:29:28 GMT

CCNA1 TCRs for AML and solid tumors High-affinity HLA-A2 restricted TCRs for the treatment of AML and several solid tumors. Cancer-testis antigen cyclin A1 (CCNA1) is an alternative A-type cyclin and is thought to promote cell proliferation (specifically at the G1/S transition) and survival, has been shown to be leukemogenic in mice. It is overexpressed in ≥50% Acute Myeloid Leukemia (AML) and ovarian cancer. This overexpression is associated with poor prognosis and shorter survival rates in AML patients. Dr. Phil Greenberg’s lab at Fred Hutchinson Cancer...

SNP panel for predicting prostate cancer-specific mortality

jbcho@fredhutch.org — Wed, 06 Dec 2023 15:25:16 GMT

Genomic Panel for Prediction of Metastatic-Lethal Prostate Cancer Progression Diagnostic combination panel of SNP, epigenetic, and genetic markers to identify metastatic-lethal prostate cancer. Dr. Stanford’s group has identified panels of single nucleotide polymorphisms (SNP), DNA methylation sites, and gene expression that classify metastatic-lethal vs. indolent prostate cancer. Prostate cancer is a clinically heterogeneous disease that often has an indolent course, but certain patients progress to metastatic- lethal disease. Additional markers are needed t...

Engineering B cells to obtain CD40 signals from antigen instead of CD40Ligand (CD40L)

jbcho@fredhutch.org — Wed, 06 Dec 2023 14:57:33 GMT

Designing universal donor B cells that will respond to antigen independently of T cell boost Methods to link CD40 signaling to antigen binding independently of CD40L binding in order to potentiate B-cell responses. Vaccines increase immunity against infections by stimulating B cells to produce antibodies against the infectious agent. In addition to infections, antibodies are also useful as treatment for different autoimmune conditions, and cancer. To mount a potent B cell response, interaction between CD40 (expressed on the surface of B cells) and CD40 ligand (CD40L; expressed on...

Optimized assay and efficient computational workflow to deliver same-day leukemia diagnostics

jbcho@fredhutch.org — Wed, 06 Dec 2023 13:12:17 GMT

Long Range Sequencing for the Detection of Fusion Genes A CRISPR-Cas9 enrichment Nanopore sequencing assay for long-read sequencing. Fusion genes occur in 30% of AML patients, resulting in distinct types of AML. Identification of these structural variants help in diagnostic classification and drive targeted therapies. Recognition of fusion variants is also important for detecting clonal heterogeneity and possibly clonal evolution. Available methods for clinical diagnosis have either low sensitivity, require long turnaround time, or the need to know the genes involved in the ...

DNA Methylation Biomarkers for Detection of Esophageal Adenocarcinoma and High-grade Dysplasia

jbcho@fredhutch.org — Wed, 06 Dec 2023 01:01:22 GMT

Novel DNA methylation biomarkers for detection of high-grade dysplasia and esophageal or junctional adenocarcinoma Minimally invasive methods and kits utilizing the methylation status of epigenetic markers that distinguish normal or Barrett’s esophageal samples from high grade dysplasia (HGD), esophageal adenocarcinoma (EAC), or junctional adenocarcinoma (JCA) samples EAC is a common and lethal cancer of GI tract. It affects ~20,000 people each year in the US and is increasing in incidence. EAC arises over time from a precancerous condition called Barrett’s esop...

Markers for identification and sorting of neoantigen specific CD4 T cells from solid tumors

jbcho@fredhutch.org — Tue, 05 Dec 2023 23:27:31 GMT

CD4+ T cell markers, compositions, and methods for cancer therapy Markers, methods, and compositions for identifying CD4+ T cells (or T cell receptor genes thereof) with tumor antigen specificity, tumor neoantigen specificity, and/or tumor-infiltrating capacity. While cancer immunotherapies have historically focused on CD8+ T cells, tumor antigen specific CD4+ T cells are required for the efficacy of immune checkpoint inhibitors in murine models and there is growing support for their importance in treating human cancers with immunotherapy. Researchers at Fred Hutchinson Cancer Ce...

MHC class II restricted T cell receptors targeting mutations in EGFR

jbcho@fredhutch.org — Tue, 05 Dec 2023 23:15:03 GMT

MHC class II restricted T cell receptors targeting mutations in EGFR Compositions and methods for targeting EGFR antigens (for e.g., to treat or manage cancer) Activating mutations in EGFR cause a subset of non-small cell lung cancer that occurs preferentially in women and non-smokers. EGFR mutated lung cancer responds to small molecule kinase inhibitors, but resistance occurs in almost all cases, and they do not benefit from existing immune therapies, so new immune therapies are necessary. While CAR and TCR immunotherapies have historically focused on CD8+ T cells, there is grow...

Modified Lee Symptom Scale (7-day severity)

jbcho@fredhutch.org — Thu, 30 Nov 2023 03:52:21 GMT

Modified Lee Symptom Scale (7-day severity) A 30 item scale to capture the symptom burden of chronic graft-versus-host disease (cGVHD). Modifications include: 7-day recall period, response options changed from bother to severity. cGVHD adversely affects patient quality of life, functional status, and survival after allogenic hematopoietic cell transplantation. A modification of the Original Lee Symptom Scale was used in the REACH3 trial, where the term “bother” is replaced with “severity” and the response options include ‘Did not have this problem, M...

Modified 7-day Lee Chronic-versus-Host Disease Symptom Scale (bother)

jbcho@fredhutch.org — Thu, 30 Nov 2023 03:48:35 GMT

Modified Lee Symptom Scale (7-day bother) The Modified 7-day Lee Symptom Scale(mLSS) is a 30-item scale with a 7-day recall period that was developed to measure the symptoms of chronic graft-versus-host-disease (cGVHD). cGVHD adversely affects patient quality of life, functional status, and survival after allogenic hematopoietic cell transplantation (HCT). The original Lee Symptom Scale is a 30-item scale that was developed to measure the symptoms of cGVHD. The original 30-item scale uses a one-month recall period, which can be challenging to measure/record as symptoms can ...

Development of Fully Human Anti-Human Siglec-8 Antibodies as Basis for Therapeutics to Treat Eosinophilic and Mast Cell Disorders

jbcho@fredhutch.org — Tue, 18 Jul 2023 11:12:09 GMT

Novel biologics targeting Siglec-8 to treat eosinophil-driven diseases Fully human mAbs, bispecific antibodies, and NK CARs that target Siglec-8. Siglec-8 is a transmembrane protein expressed on mature eosinophils, mast cells, and (to a lesser degree) basophils. Excessive eosinophil and mast cell activity have been implicated in the pathology of multiple diseases, including atopic dermatitis, chronic rhinosinusitis, chronic urticaria, and eosinophilic esophagitis. Dr. Roland Walter’s group in the Clinical Research Division at Fred Hutch has developed multiple fully hum...

Engineering B cells as a tunable source of secreted proteins

jbcho@fredhutch.org — Wed, 12 Jul 2023 11:28:35 GMT

Engineering B cells to secrete select antibodies and gene products for the treatment of diseases Method to produce B cells that can provide prolonged and tunable expression of select antibodies and gene products for the treatment of diseases (for e.g., lysosomal storage diseases) Several medical disorders are caused by an insufficiency of a gene product or a defective gene product. For example, lysosomal storage diseases are inherited metabolic disorders characterized by lack of sufficient enzymatic activity of lysosomal enzymes leading to abnormal accumulation of specific macrom...

Therapeutic targeting PRAME with mTCRCAR T cells 1 in Acute Myeloid Leukemia

jbcho@fredhutch.org — Tue, 28 Feb 2023 10:14:28 GMT

TCR mimic CAR T cells targeting PRAME/HLA-A2 Chimeric antigen receptor (CAR) that bind Preferentially Expressed Antigen in Melanoma (PRAME) ALYVDSLFFL (ALY) / HLA-A*0201 (HLA-A2) to treat PRAME-expressing cancers. PRAME is aberrantly expressed in childhood and adult AML and is absent in normal hematopoietic cells, providing an ideal target for adoptive T cell therapy. Dr. Soheil Meshinchi at the Fred Hutch has developed CAR T cells targeting the PRAME antigen in AML (referred to as PRAME mTCR CAR T cells). This CAR includes a binding domain derived from the Pr20, and a TCR m...

Natural Language Processing based smart phone application for smoking cessation

jbcho@fredhutch.org — Fri, 24 Feb 2023 16:03:40 GMT

QuitBot, an innovative chat app to assist smoking cessation A smoking cessation app that implements a novel virtual coach to answer users’ questions. Smoking remains a major public health challenge that leads to disease, premature death, and loss of productivity. Approximately 30% to 70% of smokers are interested in quitting, but in the US, less than 10% are successful at smoking cessation. Dr. Jonathan Bricker of the Public Health Sciences Division at Fred Hutch has developed an innovative smartphone app called QuitBot to help users stop smoking. QuitBot is uniq...

Candidate T cell epitopes of short H2A histone variants (novel cancer testis antigens)

jbcho@fredhutch.org — Wed, 25 Jan 2023 09:00:23 GMT

Novel Cancer/Testis Antigen: T Cell Epitopes of Short H2A Histone Variants Short H2A histone variant epitopes commonly expressed in Diffuse Large B Cell Lymphoma to be used as immunotherapy targets By analyzing data from patients with a variety of cancers, Dr. Jay Sarthy’s group at Fred Hutch Cancer Center have identified short H2A histone variants as endogenous oncohistones and novel cancer testis antigens. The identified variants in short H2A (sH2A) histone have the ability to bind to common HLA alleles, thus acting as excellent targets for immunotherapy. By comparin...

Acute Myeloid Leukemia Quailty of Life Questionnaire (AML-QOL)

jbcho@fredhutch.org — Tue, 24 Jan 2023 16:40:24 GMT

Acute Myeloid Leukemia Quallty of Life Questionnaire (AML-QOL) A validated and reliable quality of life instrument that is specific to patients with acute myeloid leukemia. Researchers at Fred Hutchinson Cancer center has developed a novel and validated quality of life instrument specifically designed for patients with acute myeloid leukemia (AML). Developed through an iterative process involving feedback from patients, medical providers, and psychometricians, the AML-QOL underwent rigorous testing and validation, including factor analysis and test-retest reliability studies...

Mesothelin directed chimeric antigen receptor T cells for treatment of acute myeloid leukemia

jbcho@fredhutch.org — Fri, 20 Jan 2023 16:39:49 GMT

Mesothelin-directed CAR T Cells for the Treatment of Acute Myeloid Leukemia CAR T cells targeting mesothelin to treat Leukemia Despite maximally intensive therapy, approximately 40% of patients with acute myeloid leukemia (AML) will relapse. An effective targeted therapy is still needed to save the lives of AML patients. Through computational interrogation of the transcriptome data, Dr. Soheil Meshinchi’s group discovered and validated mesothelin (MSLN) to be highly expressed on the cell surface of AML blasts and leukemic stem cells in a subset of AML patients. Specifi...

High Affinity MAGE-A1 T-cell Receptors

jbcho@fredhutch.org — Thu, 19 Jan 2023 16:49:29 GMT

TCR Cell Therapy Targeting MAGE-A1 High-affinity MAGE-A1-specific TCR for the treatment of multiple myeloma and solid tumors. The MAGE family are CTAs expressed in many tumor types and MAGE-A1 has been shown to directly drive tumorigenesis. Specifically, MAGE-A1 is expressed in about 50% of multiple myeloma, up to 60% in triple negative breast cancer, 30% in non-small cell lung cancer and up to 50% in ovarian cancer cells. Using a high throughput platform to identify high affinity native antigen-specific TCRs, investigators at Fred Hutch led by Dr. Chapuis ...

Chimeric and Humanized Anti-CD45 Antibody for Therapeutic Applications

jbcho@fredhutch.org — Thu, 09 Jun 2022 14:09:54 GMT

Chimeric and Humanized Anti-CD45 Antibody for Therapeutic Applications Humanized antibody offers reduced toxicity and anti-mouse antibody immunization CD45 is a transmembrane cell surface glycoprotein expressed on almost all hematopoietic cells and absent on non-hematopoietic cells. CD45 is an abundantly expressed target in most hematologic malignancies, including 85-90% of cases of acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Due to the stability of CD45 on the cell surface, it is an attractive candidate for antigen-specific immunotherapy ...

Immunosuppressive Regulatory T cells to Attenuate Autoimmune Disorders, Inflammatory Disorders, and Graft-versus-Host-Diseases

jbcho@fredhutch.org — Wed, 25 May 2022 13:54:55 GMT

Immunosuppressive Regulatory T cells to Attenuate Autoimmune Disorders, Inflammatory Disorders, and Graft-versus-Host-Diseases Methods to identify, produce, and elicit immune tolerance using TR1 cells Identification of the bona fide transcriptional and cellular control of Type-1 regulatory T (TR1) allows for the therapeutic utilization of these cells in diseases where excessive and aberrant immunity results in immune pathology. Dr. Geoff Hill’s group has developed a method to screen and identify TR1 cells that produce abundant IL-10 and Eomes. These FoxP3- immun...

Methods to avoid Graft-versus-Host Disease after allogenic transplant

jbcho@fredhutch.org — Wed, 25 May 2022 11:06:03 GMT

Methods to avoid Graft-versus-Host Disease after allogenic transplant Methods to prevent or reduce GI tract inflammation by modulating the gut microbiome and immune system Allogeneic hematopoietic stem cell transplantation (HSCT) intends to cure high-risk hematological malignancies, immunodeficiencies, metabolic disease, or a life-threatening bone marrow failure syndrome. Despite substantial advances, graft-versus-host disease (GvHD) is a major contributor to morbidity and mortality after allogenic HSCT. The intestinal epithelial cells (IECs) in the gastrointestinal (GI...

Notch ligand Delta 4 and anti-CD33 Bispecific Reagent for Treating Cancer and Other Diseases

jbcho@fredhutch.org — Mon, 04 Oct 2021 16:36:14 GMT

Novel Bispecific to Alter the Immunosuppressive Tumor Microenvironment Compositions and methods of treatment of a novel bispecific reagent that targets Notch ligand to tumor sites. The tumor microenvironment (TME) consists of the complex ecosystem where cancerous cells reside and interact with their non-malignant neighbors, including immunosuppressive myeloid cells that hinder immune control of tumors. In particular, immunosuppressive macrophages lead to the resistance of tumors to immunotherapy, a valuable treatment against many different types of cancers. Althoug...

Panel of circulating antigens as blood-based biomarkers of colon adenoma and colon adenocarcinoma

jbcho@fredhutch.org — Thu, 10 Jun 2021 11:23:17 GMT

Biomarkers for Colon Cancer Validated 5-protein panel for early detection of colon cancer and adenoma. Dr. Lampe’s laboratory has identified and validated a five protein panel for early detection of adenoma and colon cancer: BAG4, IL6ST, VWF, EGFR and glycosylated CD44. This biomarker panel has been confirmed in two independent studies of patient plasma samples in a custom high-dimensional antibody microarray containing 3,200 different antibodies: (i) pre-diagnostic plasma samples from 79 individuals diagnosed with colon cancer less than 3 years following sam...

Assay relating to COVID-19

jbcho@fredhutch.org — Thu, 03 Dec 2020 17:27:43 GMT

Neutalizing Monoclonal Antibodies Against SARS-CoV-2 for COVID-19 Screening and Treatment Development of neutralizing monoclonal antibodies (mAbs) that bind to the spike glycoprotein on SARS-CoV-2. The WHO declared COVID-19 a global pandemic as of March, 2020. The infection is caused by SARS-CoV-2, a beta coronavirus with 79.5% genome sequence identify to SARS-CoV. As of June, 2020. more than 400,000 people have died globally from COVID-19, and there remains no vaccine or approved therapeutic. The surface spike protein of SARS-CoV-2 binds ACE2 receptors on the surface of human cells...

Treatment for Glioblastoma (GBM) and other brain tumors

jbcho@fredhutch.org — Thu, 03 Dec 2020 12:23:29 GMT

Treatment of brain tumors with combinatorial NAMPT inhibitors and NAD precursors Methods to treat glioblastomas and other brain cancers with combinations of nicotinamide phosphoribosyltransferase (NAMPT) inhibitors and nicotinamide adenine dinucleotide (NAD) salvage pathway precursors. Treating brain tumors remain a challenging target due to challenges associated with crossing the blood brain barrier, accessibility, rapid spread, and tumor complexity. For all brain tumors, including benign tumors, the five-year survival rate is 33 percent. This survival rate drops to 5 perce...

Methods for HIV vaccination

jbcho@fredhutch.org — Thu, 03 Dec 2020 11:57:53 GMT

Two-Step Immunization Strategy to Elicit HIV Neutralizing Antibodies Two-step immunization process guiding the maturation of VRC01-like antibodies by accommodating a conserved position of Env, which is known to restrict CD4-binding sites. VRC01-class antibodies are considered potent and broad neutralizing antibodies (bnAbs) for HIV-1 and are important in eliciting protective immune responses in HIV vaccines. Although VRC01-class antibodies mature along different pathways, the complementarity determining region (CDR) domains similarly recognize CD4-binding sites of ...

Endothelial activation as a biomarker of toxicity after adoptive T cell therapy

jbcho@fredhutch.org — Thu, 03 Dec 2020 11:25:15 GMT

Biomarkers Predicting Risk of Cytokine Release Syndrome and Neurotoxicity Following Adoptive T Cell Therapy Risk stratification using serum-derived biomarkers to predict adverse patient responses following adoptive T cell therapies. Few assays are currently available that identify patients who are at risk of developing severe cytokine release syndrome (CRS) and neurotoxicity following adoptive T cell immunotherapy. CRS and neurotoxicity usually occur within the first 1-2 weeks after in vivo CAR-T cell activation and proliferation, complicating wide adoption of adoptive...

Microlumenal targeting of cancer cells

jbcho@fredhutch.org — Mon, 21 Sep 2020 16:50:04 GMT

Novel Method Targeting the Tumor Microenvironment as Therapeutic Treatments for Metastatic Cancers Disruption of microlumen to slow tumor growth, reduce metastasis, and increases treatment efficacy. Solid tumors and tumor cell clusters form intercellular cavities called Microlumen. These microlumen are enclosed pockets between two or more cancer cells that are bound by cell-cell junctions and separated from surrounding extracellular spaces. Cancer cells use the unique architecture of these Microlumen to restrict protein diffusion and aggregate growth facto...

Bacterial Targets as Biomarkers to Predict Increased Risk for HIV Acquisition AND Bacterial Targets as Biomarkers to Diagnose Male Urethritis

jbcho@fredhutch.org — Mon, 21 Sep 2020 16:38:58 GMT

Kit for Detecting and Classifying Sexually Transmitted Infections based on the Genitourinary Microbiome A test for detecting novel bacterial biomarkers for sexually transmitted infections (STIs). A growing need exists to increase the detection and surveillance of STIs, especially among adolescents and adults of reproductive age. STIs can cause genital neoplasia (HPV), infertility (Chlamydia) and fetal and neonatal damage (Chlamydia, Neisseria gonorrhoeae syphilis). With the availability of reliable tests, asymptomatic infections can be detected early, and ...

A disposable biospecimen collection system with integral refrigeration for preserving the phosphoproteome

jbcho@fredhutch.org — Mon, 21 Sep 2020 14:47:14 GMT

Portable and Disposable, Single-Use Snap Freezing Device to Preserve Biospecimen Integrity Tissue freezing device to ensure biopsy samples can be rapidly frozen in a clinical or field setting. Collection and processing of high-quality tissue biopsy samples are critical steps for accurate diagnosis, monitoring, and treatment. The current gold standard of snap-freezing tissue specimens in liquid nitrogen has multiple limitations, including access to liquid nitrogen, trained personnel, and/or the infrastructure to support this method. As a result, biospecimen...

Antibody, Therapeutic, and Companion Diagnostic approach targeting TRK B

jbcho@fredhutch.org — Thu, 06 Aug 2020 12:49:28 GMT

Therapeutics and Diagnostics for Cancer Targeting a Novel TrkB Splice Variant Methods to treat or diagnose a variety of cancers using agents targeting a novel TrkB splice variant Cancer-driving mutations are found across a wide range of tumor types yet are often only present in a subset of tumor cells, making early detection and subsequent treatment difficult. Many cancer types are driven by the signaling pathways downstream of tyrosine kinase receptors such as Akt, Ras, and Stat. Previously developed therapeutics targeting specific kinases have been highly profitable, yet re...

Pre-clinical and Clinical Development of Serotherapy for CMV reactivation after transplantation

jbcho@fredhutch.org — Tue, 02 Jun 2020 15:10:01 GMT

Pre-clinical and Clinical Development of Serotherapy for Cytomegalovirus (CMV) Reactivation after Transplantation Methods and tools to treat CMV reactivation in immunosuppressed patients using serotherapy Cytomegalovirus (CMV) is a common virus that infects 50-80% of the population by age 40. Although symptoms are generally mild in patients with healthy immune systems, infection or reactivation of CMV is associated with significantly lower survival after transplantation. Despite monitoring and preemptive antiviral therapy, 50-70% of CMV seropositive transpla...

Chimeric antigen receptor designs for improved recognition of low-density antigens

jbcho@fredhutch.org — Thu, 21 May 2020 16:06:03 GMT

CAR Design Improvements for the Recognition of Low-Density Antigens Methods and tools to increase CAR-T cell recognition of tumor cells expressing low density antigens Adoptive transfer of CAR-expressing T cells is an effective cancer therapy for a proportion of individuals with B cell malignancies and multiple myeloma, but efficacy is limited by relapses that stem from antigen downregulation or loss. In addition, CAR T cell therapy is also not as effective for solid tumors, where tumor-associated antigens are expressed heterogeneously and at lower levels than hematological ...

Immune Modulation of DUX4 in Cancer

jbcho@fredhutch.org — Thu, 27 Feb 2020 17:17:27 GMT

Immune Modulation of DUX4 in Cancer DUX4 as predictive biomarker and therapeutic target to enhance the effectiveness of immunotherapies Although immune checkpoint blockade therapies represent important treatments for cancer, most patients are non-responders or may relapse. The efficacy of these treatments relies on cytotoxic T-cell recognition of antigens presented by MHC Class I on tumor cells and can be reduced by suppression of antigen presentation or blunt tumor-immune interactions. Fred Hutch researchers have discovered that DUX4, a double homeobox transcripti...

Methods to Expand and Manipulate Hematopoietic Stem and Progenitor Cells

jbcho@fredhutch.org — Thu, 19 Dec 2019 16:06:12 GMT

Methods to expand and manipulate hematopoietic stem and progenitor cells Culture strategies for cost effective, ex vivo expansion of hematopoietic stem and progenitor cells (HSPCs) with enhanced in vivo repopulating ability. HSPCs can be used to treat over 70 types of diseases including a variety of hematological disorders through transplantation and genetic therapies. Insufficient numbers of HSPCs introduced during transplantations prolong engraftment which can limit the use of single-unit patient samples. Ex vivo expansion increases the dose of HSPCs and promotes...

Random Codon Mutant Libraries Created by PCR Using Synthetic Nucleotides

jbcho@fredhutch.org — Tue, 22 Oct 2019 13:27:27 GMT

Codon-Mutant Libraries of Protein-Coding Genes Technique that mutates entire genes at the codon level at a controlled rate, compared to existing error-prone PCR methods that achieve this on the nucleotide level Random mutant libraries of genes are used in a wide variety of molecular biology and bioengineering applications. Current techniques (such as error-prone PCR and its variants) are well suited for introducing mutations at the nucleotide level. PCR with oligonucleotides containing degenerate bases at certain positions are well suited for creating rando...

MAIT CTLA4

jbcho@fredhutch.org — Tue, 22 Oct 2019 12:15:43 GMT

MAIT Cell Immunomodulation for Targeted Treatment of Inflammatory Diseases MAIT cells undergo targeted therapeutic exploitation to alter CTLA-4 expression and dampen inflammatory responses. Mucosal-associated invariant T (MAIT) cells are non-conventional T cells that localize within inflamed tissue. Upon activation, MAIT cells act as effector cells with both cytotoxic and pro-inflammatory properties. The Prlic Lab determined MAIT cells have a unique transcriptional signature based on whether located within the blood or inflamed tissue. Conventional T cells ...

Multimeric NKG2D for immunomodulation

jbcho@fredhutch.org — Mon, 21 Oct 2019 14:26:18 GMT

NKG2D Biologic to Reduce Immune Cell Activation A multimeric decoy to block activation of NKG2D and treat autoimmune and inflammatory diseases, and for use in vaccine development. Dr. Roland Strong and Dr. Martin Prlic have developed a multimeric NKG2D decoy that will bind all NKG2D ligands and block the NKG2D pathway. NKG2D is a receptor expressed by immune cells which activates the immune cell upon ligand binding. While stimulation of NKG2D can be beneficial in some circumstances, its activation is associated with several autoimmune and inflammatory diseases such...

Quantitative method for accurately counting DTCs, CTCs, and ctDNA in a biological sample – or any cell “tagged” with DNA insert

jbcho@fredhutch.org — Fri, 04 Oct 2019 08:10:37 GMT

Barcoding for the Tracking and Quantification of DNA System and methods for digital quantification and tracking of cells and DNA including, DTC, CTCs, and ctDNA. Dr. Bielas and colleagues have been working on developing methods to quantify DNA and reduce background noise to better track, sequence, and quantify DNA. Genetic constructs are created using repeats of unique genetic sequences separated by restriction enzymes. These constructs act as barcodes to tag and track cells and DNA including mitochondrial DNA (mtDNA), disseminated tumor cells (DTCs), circulating tumor cells (CTCs), ...

NOD2 acts as a master regulator of regeneration pathways in the thymus

jbcho@fredhutch.org — Fri, 04 Oct 2019 08:09:42 GMT

NOD2 Mediated Thymic Regeneration Boosts Compromised Immune Function Promotion of thymic regeneration through reduction or inhibition of nucleotide-binding oligomerization domain-containing protein 2 (NOD2) by upregulating regenerative molecules (e.g., interleukin (IL)-22, IL-23, and bone morphogenetic protein 4 (BMP4)). As the primary site for T cell development, thymic regeneration is critical for the renewal and development of immune competence following stress (e.g., conditioning required for hematopoietic stem cell transplant or cytotoxic cancer treat...

Immunostimulatory Capacity of Two Anti-Human NKG2D Monoclonal Antibodies

jbcho@fredhutch.org — Wed, 02 Oct 2019 14:11:24 GMT

Monoclonal NKG2D Antibodies for the Treatment of Autoimmune and Inflammatory Disorders Two anti-human NKG2D monoclonal antibodies to specifically target and/or inhibit the NKG2D receptor on immune cells (e.g., CD4+ T cells). A precise balance of effector T cell activity is required to maintain effective immune surveillance without initiating an autoimmune reaction. NKG2D is an activating receptor that interacts with MHC Class I MICA and MICB glycoproteins. Drs. Spies and Groh made the surprising discovery that rheumatoid arthritis and other immunoprolifera...

Novel Bispecific Antibody Targeting CD45

jbcho@fredhutch.org — Thu, 25 Oct 2018 16:12:43 GMT

Pretargeted Radioimmunotherapy for the Treatment of of Acute Myeloid Leukemia An anti-CD45 bispecific antibody delivering targeted radioimmunotherapy to treat acute myeloid leukemia (AML), while avoiding systemic toxicity. Pretargeted radioimmunotherapy (PRIT) is a two-step approach that delivers radioactivity separate from the initial targeting step. CD45 is a great target for PRIT as it is expressed on nearly all hematopoietic cells and negligibly expressed on non-hematopoietic tissues. Therapeutic efficacy was shown in AML previously when targeting CD45 using a streptavidin-bioti...

CD38 and BCMA Bispecific Antibody Pretargeted Radioimmunotherapy for Multiple Myeloma and other B Cell Malignancies

jbcho@fredhutch.org — Mon, 20 Aug 2018 16:17:05 GMT

Pretargeted radioimmunotherapy for the treatment of Multiple Myeloma & B cell malignancies Anti-CD38 and anti-BCMA bispecific antibodies deliver targeted radioimmunotherapy and avoid systemic toxicity. Pretargeted radioimmunotherapy (PRIT) differs from conventional RIT in that a nonradioactive bispecific targeting antibody is first administered allowing for localization in tumor sites. Then a low molecular weight radioactive moiety (such as Y90) is added facilitating rapid tumor penetration, capture, and retention of Y90 by the pretargeted antibody. The rapid clearance of unboun...

Digital quantification of random mitochondrial DNA deletions

jbcho@fredhutch.org — Thu, 08 Feb 2018 16:10:43 GMT

Digital Deletion Detection and QuantiSize This method allows for measurement of rare deletions, while concurrently gathering information about size and homogeneity of the unknown template. Dr. Bielas has developed a sensitive, quantitative method to detect rare mutations in genomic and mitochondrial DNA. The main strategy is a three-step process starting with targeted enrichment for deletions, followed by amplification, and then analysis for quantification or characterization. This method shows improvements in specificity, sensitivity, and accuracy over other avail...

Luteinizing hormone as a means of promoting HSC expansion ex vivo

jbcho@fredhutch.org — Wed, 04 Oct 2017 16:28:59 GMT

Methods to Target Hematopoietic Stem Cells for Ablation or Expansion Luteinizing hormone receptor (LHR) binding agents and luteinizing hormone (LH) agonists to target and expand HSCs. Hematopoietic stem cell transplant (HCT) has been curative for many cancer malignancies and monogenetic diseases. However, current clinical limitations include small number of true HSCs in the transplant graft and the need for genotoxic myeloablative conditioning regimens. Teams at Fred Hutch and Memorial Sloan Kettering have discovered a novel role of LH in HSC biology and have demon...

Rational design of alpha-helical tandem repeat proteins with closed architectures

jbcho@fredhutch.org — Wed, 17 May 2017 14:35:08 GMT

cTRPs: Circular Tandem Repeat Protein Platform Methods to create circular tandem repeat proteins (cTRPs) to display a wide variety of functional protein domains Protein engineering is a growing field which produces new approaches to the basic study of protein structure and function as well as facilitates opportunities to produce and design novel proteins. One such attractive target for engineered proteins are Tandem Repeat Proteins (TRPs), which are soluble and thermostable proteins that contain multiple repeated peptide sequences and have evolved to bind many different types of ...

IL-17c For Prevention of Neuropathy and Axonal Guidance

jbcho@fredhutch.org — Wed, 17 May 2017 14:35:07 GMT

Novel Treatment for Neuropathies and Neurodegeneration Use of IL-17c as a novel neurotrophic factor can be applied to treat neurodegenerative disorders. Dr. Corey and his colleagues have discovered that Interleukin-17c, previously only known as a cytokine, is secreted by keratinocytes during HSV infection and acts as a neurotrophic factor for neural cells. They demonstrated for the first time, that IL-17c can promote neural cell survival, neural growth, and axon guidance. Use of IL-17c as a novel neurotrophic factor can be applied to treat neurodegenerative disorders, for example, ne...

Multimerized HIV gp120s

jbcho@fredhutch.org — Wed, 17 May 2017 14:35:06 GMT

Multimerized HIV gp120s for Vaccine Development An engineered HIV Env glycoprotein that improves antibody-recognition potential for HIV vaccine development. Dr. Leo Stamatatos and Dr. Roland Strong have developed a unique and promising approach to developing an effective HIV vaccine by engineering an HIV Env glycoprotein using specific gp120 modifications and multimerization strategies. This multimerized gp120 expands the germline (gl) VRC01-class antibody- recognition potential of the Env, as desired in vaccine development for HIV. HIV-1 broadly neutralizing antib...

New FSHD DUX-4-induced Candidate Biomarkers and Immune Response Regulators

jbcho@fredhutch.org — Wed, 17 May 2017 14:35:05 GMT

Gene Expression Biomarkers to Track Facioscapulohumeral Dystrophy Disease Progression DUX4-dependent gene expression is a major molecular signature of Facioscapulohumeral Dystrophy (FSHD). Facioscapulohumeral dystrophy (FSHD) is a human muscular dystrophy that initially affects the muscles of the face and upper extremities, but can progress to affect most skeletal muscles. Despite genetic evidence suggesting that DUX4 mRNA expression is necessary for FSHD, due to its low abundance in muscle biopsies, its critical role in disease pathogenesis has been questioned. Researchers in ...

Agents that target Runx3 or Runx3-dependent pathways for treatment of pancreas cancer

jbcho@fredhutch.org — Wed, 17 May 2017 14:35:05 GMT

Targeting Runx3 for the Treatment of Pancreatic Cancer Novel therapeutic target to prevent metastasis of pancreatic cancer. Dr. Hingorani and colleagues have discovered that RUNX3 controls the balance between local growth and metastasis in pancreatic ductal adenocarcinoma. By varying RUNX3 expression levels in vitro they found that RUNX3 functions to promote metastatic programs, and by silencing RUNX3 they observed decreased metastasis. In vivo experiments demonstrated that RUNX3 depletion significantly impairs the ability of tumor cells to seed and support seconda...

Cancer expression of the NKG2D lymphocyte receptor together with its ligands and promotion of tumorigenesis

jbcho@fredhutch.org — Wed, 17 May 2017 14:35:04 GMT

NKG2D-Targeted Therapy for Ovarian Cancer Therapeutic for ovarian cancer that targets NKG2D ligands and prevents binding and stimulating the NKG2D receptor. Normally expressed by immune cells, subsets of human cancer cells co-opt expression of the NKG2D receptor to exploit the presence of its ligands on cancer cells for oncogenic/tumorigenic stimulation. One such cancer subtype is ovarian cancer (OC). Dr. Thomas Spies has demonstrated the ability to interfere with cancer growth by interfering with NKG2D ligand binding, while Dr. Roland Strong and Dr. Martin Prlic h...

A Method For The Treatment Of Obesity Using Immunotherapy With Monoclonal Antibodies, Endogenous T Cells, Or T Cells Modified To Express A Chimeric Antigen Receptor Specific For The Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1)

jbcho@fredhutch.org — Wed, 17 May 2017 14:35:03 GMT

Immunotherapy for the Treatment of Obesity A method for using immunotherapy to identify, target and eliminate fat cells. Currently, there are no treatments for obesity that directly target and eliminate fat cells (adipocytes). Dr. Stanley Riddell, in collaboration with colleagues at the NIH, have demonstrated that an anti-ROR1 CAR T is able to specifically recognize mature adipocytes and exert cytolytic activity. Interestingly, the only normal tissue that expresses the ROR1 protein on the surface of the cell is preadipocytes, progenitor fat cells, which make them a...