By directed evolution, various amino acid substitutions which impart greater brightness to the UnaG fluorescent protein were developed. With certain combinations of mutations, the improved UnaG protein has brightness 100 times greater than the original parent sequence. Bi-molecular fluorescence complementation assays using the improved UnaG variants provide strong signal and high resolution and provide powerful tools for detecting protein-protein interactions (PPIs). PPI detection tools for various important proteins are provided. These assays enable highly efficient screening of putative PPI modulators and the identification, verification, and development of therapeutics that disrupt pathological PPIs.

Provided are methods and articles of manufacture for use with cell therapy for the treatment of diseases or conditions, e.g., cancer, including for predicting likelihood of the subject responding to a therapy, such as a cell therapy, e.g., a chimeric antigen receptor (CAR) T cell therapy. In some aspects, the predicting is based on detecting certain biomarkers of immune cells associated with and/or that correlate with response following administration of the therapy. The methods generally involve detecting a marker by assaying a biological sample from a subject that is a candidate for treatment, optionally with a cell therapy, to determine if the subject is likely to respond to the therapy. The present disclosure also provides methods for treating a subject having a disease or condition, in some cases involving administration of the cell therapy, based on assessment the biomarker. Also provided herein are reagents and kits for performing the methods.

The present invention relates to efficient methods for providing antigen-specific lymphoid cells. These lymphoid cells may be used to provide antigen specific T cell receptors having a defined MHC restriction and to identify immunologically relevant T cell epitopes. Furthermore, the present invention relates to antigen-specific T cell receptors and T cell epitopes and their use in immunotherapy.

This disclosure relates to predicting the carcinogenicity of compounds. More in particular, this application discloses methods to detect whether a compound is a non-genotoxic carcinogen and methods to discriminate between genotoxic and non-genotoxic carcinogens based on in vivo stem cell proliferation patterns in flatworms.

A molecular marker for detecting a cancer stem cell in a cell mass which is a subject of interest, wherein the molecular marker can be detected in a cancer stem cell contained in the subject of interest but cannot be detected in a normal cell and a cancer cell that is different from a cancer stem cell; a method for determining the presence or absence of a cancer stem cell in a subject of interest by using the molecular marker as an measure; a kit for determining the presence or absence of a cancer stem cell, which comprises at least a reagent for detecting the molecular marker; a polypeptide encoded by the molecular marker; an antibody capable of recognizing an epitope of an expression product of a gene derived from the molecular marker; a nucleic acid capable of inhibiting the expression of the molecular marker; and a nucleic acid vaccine comprising a gene derived from the molecular marker.

The present invention relates to methods and kits for prognosing, treating, and managing treatment of cancer in a subject. The methods involve selecting a subject having cancer and obtaining, from the selected subject, a sample containing exosomes or an S100 molecule containing sample. The exosomes or S100 molecule containing sample, respectively, are then contacted with one or more reagents suitable to detect higher or lower levels or the presence or absence of one or more integrins on said exosomes or higher or lower levels or the presence or absence of one or more S100 molecules in the S100 molecule containing sample. The cancer is then prognosed, treatment is administered, or treatment is managed.

An in vitro assay is provided for determining the effect of an immune cell on a cell from an infectious or neoplastic disease. Also provided is an in vitro assay for determining the effect of an activated CD8.sup.+ T-cell on a sensitized melanoma cell. A method for improving the specific cytolytic activity (SCA) of an immune cell comprising contacting an immune cell with an antigen and an antigen-independent pro-inflammatory agent is provided. A method for ex vivo expansion of antigen-specific CD8.sup.+ T-cells with enhanced specific cytolytic activity (SCA) comprising culturing the antigen-specific CD8.sup.+ T-cells in a suitable culture media comprising an amino acid. An in vitro assay is provided for determining the effect of an immune cell on a cell from an infectious or neoplastic disease. A method of treating a subject suffering from an infectious or neoplastic disease with immuno therapy is described.

A method to detect a biomarker in saliva wherein the biomarker is an extracellular mRNA, comprises detecting the extracellular mRNA in the cell-free saliva; transcriptome analysis of saliva comprises detecting a transcriptome pattern in the cell-free saliva; a method to detect genetic alterations in an organ or in a gene in the organ by analyzing saliva, comprises detecting a transcriptome pattern and/or the mRNA profiling of the gene in cell-free saliva; a method to diagnose an oral or systemic pathology disease or disorder in a subject, comprises: detecting profile of a biomarker associated with the pathology disease or disorder, in particular mRNA and/or protein, in cell-free saliva and/or serum; kits comprising identifier for at least one biomarker for performing at least one of the methods; and use of salivary biomarker salivary and/or serum mRNAs as biomarkers for oral and/or systemic pathology, disease or disorder.

The present disclosure provides methods for producing activated type I sulfatases, or functional fragments thereof, using Formylglycine Generating Enzymes (FGEs). Also featured by the disclosure are recombinant fungal (e.g., Yarrowia lipolytica) cells expressing the FGE and, in some embodiments, type I sulfatases, or functional fragments thereof, and/or additional accessory enzymes. The disclosure also provides activated type I sulfatases or functional fragments thereof, made by the disclosed methods and therapeutic methods using the activated type I sulfatases or functional fragments thereof.

Disclosed herein are methods of treating, reducing the incidence of, or preventing one or more activities in or of a cancer cell, methods of treating, reducing the incidence of, or preventing migration or metastasis of a cancer cell, methods of treating, reducing the incidence of, or preventing a cancer by reducing tumor associated macrophages (TAMs) or their migration, and methods of treating, reducing the incidence of, or preventing a cancer (including metastatic cancer), for example, with an inhibitor of Motile Sperm Domain containing Protein 2 (MOSPD2). Also disclosed are inhibitors of MOSPD2 (e.g., anti-MOSPD2 antibodies or antigen binding fragments thereof) and pharmaceutical compositions containing MOSPD2 inhibitors. Also disclosed are methods for the prediction, diagnosis, or prognosis of cancer, cancer metastasis, tumor progression, or tumor invasiveness in a subject.