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Humanized, potent monoclonal antibodies against murine and human integrin avb8 for cancer immunotherapy and prevention of corneal scarring after cataract surgery

Immunotherapy has revolutionized the treatment of many cancers, but even for the most sensitive tumor types most patients do not respond to current immunotherapy regimens. One major block to effective anti-tumor immunity is inhibition of the function of effector T cells by active TGFβ in tumors. For this reason, several major pharmaceutical companies have invested substantial resources in developing inhibitors of TGFβ ligands or TGFβ signaling to enhance anti-tumor immunity. However, because TGFβ isoforms (TGFβ1, 2 and 3) play multiple important homeostatic roles, highly effective inhibition of TGFβ function causes severe toxicity, as seen by the embryonic or perinatal lethality of knockout of each of the 3 mammalian TGFβs. Even the relatively ineffective TGFβ inhibitors that have entered clinical trials have been withdrawn because of unacceptable toxicity (cardiac valve thickening and skin cancer). We have thus spent the past 20 years developing drugs targeting TGFβ activating integrins, which only activate a small fraction of extracellular latent TGFβ in precise contexts relevant to specific diseases, with the goal of increasing precision and greatly reducing the potential for toxicity. 

Control Of Chimeric Antigen Receptor Activation By Their Hinge And Transmembrane Domains

UCSF inventors have created a hybrid sequence that, when engineered into Chimeric Antigen Receptor (CAR) T cells, promotes activation of the cells solely with CD28 antibodies or CD28 ligands. The sequence is a combination of the CD28 or IgG4 hinge region and the CD28 transmembrane, and represent a new opportunity to control T cell function. The technology has been tested in vitro with in vivo studies ongoing. The added functionality through this sequence has potential to promote survival and homeostasis of CAR T cells in the absence of CAR target and improve the specificity and toxicity profiles of current CAR T therapies. 

Blood Based T Cell Biomarker For Cancer Diagnosis And Treatment

In cancer care, specific characteristics of T cells can be used to measure a patient’s response to immunotherapy. Using single-cell RNA-sequencing coupled with TCR sequencing, scientists at UCSF and Harvard detected CD8+ T cell clones shared between blood and tumor in mice and melanoma patients, characterized these matching clones in blood and tumor, and identified potential biomarkers for their isolation in the blood. Their method reveals specific protein signatures (biomarkers) on the surface of T cells that can be therapeutically targeted to treat melanoma and other forms of cancer. It presents a very attractive alternative to obtaining invasive biopsy samples from the tumor, and can be done much more quickly.  

Anti-Human SULF2 monoclonal antibodies for research applications

Sulfatase 2 (SULF2) is an extracellular sulfatase that acts on heparan sulfate proteoglycans.  It is overexpressed and pro-oncogenic in many cancers. Its overexpression in the liver is linked to dyslipidemia and fatty liver disease. This invention describes a panel of monoclonal antibodies that are validated for immunocytochemical staining, biochemical analysis and functional studies of human SULF2.   

Covidseeker. Digital Contact Tracing And Hotspotting In Real-Time

UCSF PIs developed a novel software platform for COVID-19 contact tracing and hotspotting called COVIDseeker. Covidseeker looks back in time and may be able to recreate people’s movements when infection rates were rising and falling in the spring and summer of 2020, giving epidemiologists an invaluable source of data as they try to predict what is going to happen in the fall and winter.This digital health invention has applications broader than COVID-19. The software can potentially be leveraged for other infectious diseases, treating obesity, and controlling smoking or alcohol addiction by showing where and when people are when they smoke, what are the triggers and how their location contributes to the risk of developing a particular disease.

XYZeq – Spatially-Resolved Single Cell Sequencing

Researchers at UCSF have developed XYZeq, a method for coupling a cell’s spatial location with single-cell sequencing. Single-cell genomic techniques have emerged as powerful approaches to further our understanding of disease states and cellular heterogeneity. Single-cell imaging methods gain spatial information, but lack throughput and detailed transcriptomic information. Current single-cell sequencing approaches require dissociation of cells during preparation, as a result cannot record a cell’s physical location. UCSF researchers eliminate this step using XYZeq, a new scRNA-seq process that incorporates the benefits of single-cell imaging techniques with single-cell sequencing, without an imaging step. XYZeq simultaneously discerns the location and gene expression of a single cell residing within a complex tissue microenvironment. The technology has been validated in a laboratory setting.