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A novel method for increasing MHC presentation of oncogene derived neoantigens

The invention describes a platform technology that increases MHC presentation of oncogene derived peptide neoantigens that do not normally occur in the cell. The platform has already been used to identify a method of increasing KRAS G12 D/V derived peptide presentation on MHC- I.

Bioengineered RNA Molecules for Cancer Therapy

Researchers at the University of California, Davis have developed a method to use biologic RNA molecules for cancer research and therapy.

Bioengineered Let-7c Therapy for HCC Treatment

Researchers at the University of California, Davis have developed a bioengineered, RNA-based treatment for advanced liver cancer and hepatocellular carcinoma (HCC).

Monoclonal Antibodies Specific to Canine PD-1 and PD-L1

Researchers at the University of California, Davis have developed monoclonal antibodies with multiple applications relevant to canine PD-1 and PD-L1.

Label-free Rapid Pathologic Tissue Diagnosis During Surgery

Researchers at the University of California, Davis have developed a method to rapidly identify regions of diseased tissue while a surgery is being conducted.

Use of UBA7 and its Regulated Genes as Novel Biomarkers in Treating Human Cancers

Human Ubiquitin-like modifier-activating enzyme 7 (UBA7) is a protein is involved in protein modification, specifically involving the pathway for protein ubiquitination. The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. UBA7  encodes a member of the E1 ubiquitin-activating enzyme family. Moreover, ubiquitination and ubiquitin-like post-translational modifications (PTMs) regulate activity and stability of oncoproteins and tumor suppressors. Biomarkers are very important as companion diagnostic tools to guide clinical practice in treating human cancers, especially for targeted therapies. In the era of precision medicine, it is important for development companion diagnostic tools that can guide clinical practice for treating human cancers using targeted therapies.

Potent and Selective Peptide Inhibitors for MMP-2

Prof. Min Xue and his colleague at the University of California, Riverside have developed peptide-based selective MMP-2 inhibitors with nanomolar activities. Unlike known MMP inhibitors, n-TIMP-2 and GM6001 that inhibit a broad spectrum of the MMP family, these peptide inhibitors do not exhibit off-target effects with other MMP family members such as MMP-9.  Fig. 1 shows how a proMMP2 inhibitor (orange) interferes with the protein-protein interaction (PPI) between proMMP2 and TIMP2 (tissue inhibitor of metalloproteinases 2). This PPI inhibition blocks the TIMP2-assisted proMMP2 activation process and thereby results in lower levels of active MMP2. Fig. 2 shows the novel UCR MMP-2 peptide binds to proMMP2 with an Kd of 2.3 nM and inhibits MMP2 activation with an IC50 of 20 nM.  

Neoantigen-specific antibodies for chemically directed immune targeting of KRAS tumors

UCSF scientists have discovered novel antibodies that can specifically and selectively recognize tumor-derived neoantigens. The antibodies can be used for IgG, BiTE or CAR-T-based targeted immunotherapy and small molecule-based directed immune targeting via combination therapy. This dual therapeutic approach has the potential to specifically recognize and treat KRAS (G12C) cancer cell populations with high specificity, significantly improve cancer treatment outcomes, and overcome risk of treatment resistance in patients.

A Tumorigenic Index to Determine Liver Cancer Initiation and Prognosis

The incidence and mortality of liver cancer, mainly hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), are increasing rapidly worldwide. Diverse risk factors for primary liver cancer have been identified, including infection of hepatitis B virus (HBV) and hepatitis C virus (HCV), alcohol abuse and non-alcoholic steatohepatitis (NASH) as well as intake of aflatoxin B1. Consistent with the complex and multifactorial etiologies, multi-omics analyses of human HCC and ICC samples have identified vast genomic heterogeneity, molecular and cellular defects, metabolic reprogramming, and subtypes of tumors as well as altered tumor microenvironment in the liver. However, it remains to be determined if any common molecular signatures in the transcriptomes exist for liver cancer, despite their considerable genomic heterogeneity. Furthermore, little is known about the kinetics and fashions, either gradual accumulation or dramatic transition, in generation of cell-intrinsic and -extrinsic signals that are intertwined to drive malignant transformation of hepatocytes and tumor initiation.

Computational Cytometer Based On Magnetically-Modulated Coherent Imaging And Deep Learning

UCLA researchers in the Department of Electrical & Computer Engineering have designed and built a computational cytometer capable of detecting rare cells at low concentration in whole blood samples. This technique and instrumentation can be used for cancer metastasis detection, immune response characterization and many other biomedical applications.

IFN-gamma Receptor On T Cell Immunotherapy

This invention identifies that tumor-specific T cells are susceptible to immunotherapy induced IFN-gamma toxicity in low tumor burden circumstances, and provides a novel method for rescuing those tumor-reactive T cells and anti-tumor immunity through disruption of IFN-gamma signaling.

Switchable Chimeric Antigen Receptor-Engineered Human Natural Killer Cells

The existing CAR-engineered T cell-based (CAR-T) therapy represents one of the most successful immunotherapy approaches developed in recent years. Most CAR-T cell therapy has been used clinically to treat hematological malignancies by targeting the B cell-specific antigen, CD19. However, this approach is not without limitations due to toxicities such as by neurotoxicity or cytokine release syndrome. Additionally, CAR-T cells function only as autologous cells due to graft-versus-host disease that would develop if cells were obtained from another person. Therefore, CAR-T cells must be produced on a patient-specific basis. NK cells, on the other hand, function as allogenic cytotoxic effector cells that do not have to be utilized on a patient-specific basis and are proven to be less toxic since they do not cause cytokine release syndrome, neurotoxicity, or graft-versus-host disease. For these reasons, CAR-engineered NK (CAR-NK) cells have increasingly attracted interest as an alternative CAR-cell therapy. However, there exist other unmet challenges. Targeting CAR-based therapies against solid tumors has been challenging due to the lack of truly tumor-specific antigens as most targets are shared by non-malignant cells and can cause toxicity due to “on-target, off-tumor” effects.” A fine-tunable CAR therapy is useful to better identify and target tumors while limiting this toxicity.

Use of Gene Therapy to Treat Joint Disease and Synovial Tumors

The National Center for Advancing Translational Sciences and Genetic and Rare Diseases Information Center characterizes Pigmented villonodular synovitis (PVNS) as a rare disease estimated to occur in ~ 5-6 people out of 100,000. This locally invasive tumor most often occurs in younger adults and causes severe damage to joints. The first line of treatment is surgery but at least 50% of patients require multiple surgeries over many years due to re-growth of the tumor.

Prevention Of Liver Disease By Preventing Degradation Of SRSF3

The global increase in obesity over the past few decades has caused a corresponding increase in NAFLD and its more severe form non-alcoholic steatohepatistis (NASH). Both NAFLD and NASH are associated with liver insulin resistance, non-alcoholic cirrhosis, and for the development of HCC. HCC is currently ranked as the fifth most common cancer worldwide and has a high mortality. It usually arises after years of liver disease and inflammation either due to chronic hepatitis B or C virus (HBV/HCV) infection, or alcoholic and non-alcoholic cirrhosis. SRSF3 is the smallest member of the SR protein family that function to promote RNA splicing by recruiting components of the spliceosome at constitutive and alternatively spliced exons. SRSF3 has also been ascribed a number of cellular functions including controlling cellular proliferation, as it is regulated during G1/S by the E2F transcription factor and controls the G2/M transition of immortal rat fibroblasts.  Recent findings demonstrating that loss of SRSF3 triggers metabolic changes, hepatic fibrosis, and increased liver inflammation that are all features of early liver disease. The loss of expression of SRSF3 in the liver leads to chronic liver damage, fibrosis and eventually to hepatocellular carcinoma (HCC). In fact, SRSF3 is reduced in samples of human HCC as well as NAFLD, NASH and cirrhosis. SRSF3 protein levels are controlled in part by the conjugation of SRSF3 to an ubiquitin-like protein NEDD8 on Lys11, which results in its degradation by the proteasome in response to stress.

Identification Of Pan-Cancer Small Cell Neuroendocrine Phenotypes And Vulnerabilities

UCLA researchers in the Department of Molecular and Medical Pharmacology have developed a classifier for the identification and treatment of small cell neuroendocrine cancers and small-round-blue cell tumors not previously identified.

Improvement To Retroviral Vectors Containing The Human Ubiquitin C Promoter

UCLA researchers in the Department of Molecular Biology have developed a lentiviral vector, “pCCLc-roUBC”, containing the cellular promoter from the human ubiquitin C gene (UBC), to improve transgene expression in retroviral vectors.

HRas Selective Depalmitoylating Drugs

HRas is a member of the Ras family of GTPases, which function as key regulatory proteins in cell differentiation, proliferation, and survival. Mutations in HRas are associated with several cancers, as well as Costello syndrome, a severe congenital disorder for which there is no cure. Therefore, there is significant interest in developing therapeutics which target HRas signaling. However, Ras proteins are challenging to target

A Microfluidic Single-Cell Pairing Array for Studying Cell-Cell Interaction in Isolated Compartments

Cell interactions are fundamental to biological processes. Microfluidics provides a reliable platform to study these intricate phenomena. The researchers have developed a microfluidic trapping array which efficiently pairs single cells in isolated compartments in an easy to operate manner to study cell-cell interaction, especially at single-cell level.

Improved Highly Potent Specific Human Kunitz Inhibitor of Fibrinolytic Enzyme Plasmin

UCLA researchers in the School of Medicine have developed mutant polypeptides of the tissue factor pathway inhibitor-2 (TFPI-2) Kunitz domain 1 (KD1), which can serve as potent inhibitors of fibrinolysis.

Gelatin Methacryloyl Based Microneedle

UCLA researchers in the Department of Bioengineering have developed gelatin methacryloyl microneedles (GelMA MN) for minimally invasive, sustained transdermal drug delivery.

Brain-Specific Kinase Inhibition to Mitigate Systemic Toxicity

The goal of this invention is to overcome the challenges of previous approaches by selectively targeting treatments to the CNS without peripheral toxicity. Kinase inhibition is targeted to the central nervous system (CNS) by combining brain-permeable kinase inhibitors and a brain-impermeable blocking molecule.

Chimeric Kinase Inhibitors with Increased Activity

This invention describes newly generated kinase inhibitors that demonstrate enhanced and attenuated action over their parent kinase inhibitors. These molecules can be used alone but, when combined with novel blocking molecules, the action of these chimeric kinases can be targeted for action in the central nervous system (CNS).

TRM: Mouse Mammary Tumor Virus-PyMT Transgenic Mice

Transgenic mouse models that develop spontaneous mammary adenocarcinomas have proven valuable in revealing molecular mechanisms underlying tumorigenesis and metastasis . Models target specific pathways depending on the transgene being expressed under the control of the mouse mammary tumor virus long terminal repeat (MMTV-LTR) or whey acid protein (WAP) mammary gland promoters and thereby replicate genetic defects in subsets of human tumors.

NOVEL ANTIBODIES AGAINST EPHA2 FOR RESEARCH, DIAGNOSIS, AND TREATMENT OF CANCER

A novel monoclonal human antibody specific to the cell-surface exposed protein EphA2, which is over-expressed in many forms of cancer and is a validated therapeutic target.

TRM:Murine Pancreatic Cancer Cell Lines

Brief description not available

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