Abstract: Systems and methods to link CD40 signaling to antigen binding, independently of CD40 ligand binding are described. The systems and methods include fusion proteins including an extracellular antigen binding domain linked to an intracellular CD40 signaling domain.

Abstract: Mutated and/or truncated malarial circumsporozoite proteins (CSP) and associated nucleic acids that are more stable and highly expressed in mammalian cells are described. The mutated and/or truncated CSP and associated nucleic acids can be expressed to produce malaria vaccine antigens.

Abstract: Methods to create barcoded influenza viruses without disrupting the function of the viral proteins and the proper packaging of the viral genome segments are described. The barcoded influenza viruses can be used within deep mutational scanning libraries to map influenza resistance mutations to therapeutic treatments. The libraries can also be used to predict influenza strains that may become resistant to therapeutic treatments and/or more easily evolve to infect new species. The libraries include features that allow efficient collection and assessment of informative data, obviating bottlenecks of previous approaches.

Abstract: Hematopoietic stem/progenitor cells (HSPC) and/or non-T effector cells are genetically modified to express (i) an extracellular component including a ligand binding domain that binds a cellular marker preferentially expressed on an unwanted cell; and (ii) an intracellular component comprising an effector domain. Among other uses, the modified cells can be administered to patients to target unwanted cancer cells without the need for immunological matching before administration.

Abstract: Provided herein are methods to reduce tumor cell proliferation in a cancer patient by administering an antibody that binds angiopoietin-like 7, wherein administering the angiopoietin-like 7 antibody can reduce necrosis formation, metastasis formation, and circulating tumor cells.

Abstract: The present disclosure provides compositions and methods for the delivery of immune cells to treat un-resectable or non-resected tumor cells and tumor relapse. The compositions comprise (i) a structure comprising an injectable polymer or scaffold comprising pores; (ii) lymphocytes disposed within the structure, (iii) at least one lymphocyte-adhesion moiety associated with the structure; and (iv) at least one lymphocyte-activating moiety associated with the structure, and optionally an immune stimulant.

Abstract: Implantable scaffolds that treat solid tumors and escape variants and that provide effective vaccinations against cancer recurrence are described. The scaffolds include genetically-reprogrammed lymphocytes and a lymphocyte-activating moiety.

Abstract: A method for detecting the binding of a chromatin-associated factor of interest to a sequence of chromatin DNA in a cell, including: contacting a permeabilized cell or nucleus with a specific binding agent that specifically recognizes the chromatin-associated factor of interest, wherein the specific binding agent is linked to a nuclease that is inactive or an activatable transposome; activating the nuclease or transposase, thereby excising the sequence of chromatin DNA bound to the chromatin-associated factor of interest; isolating the excised DNA; and determining the sequence of the excised DNA, thereby detecting binding of a chromatin-associated factor of interest to a sequence of chromatin DNA in the cell.

Abstract: Provided herein are kits and methods for detecting, monitoring, and classifying a nongonococcal urethritis (NGU) infection in a male subject based on a genitourinary microbiome of a subject, as well as related methods of treating. Also provided are kits and methods for classifying a risk of human immunodeficiency virus (HIV) infection in a subject based on a genitourinary microbiome of a subject, as well as related methods of preventing infection.

Abstract: Sequential immunization strategies to guide the maturation of antibodies against the human immunodeficiency virus (HIV) are described. The sequential immunization strategies utilize an HIV envelope protein (Env) that binds germline (gl) B cells as a first (prime) immunization and an Env with a functional glycosylated N276 as a second (boost) immunization. The sequential immunization strategies successfully elicit neutralizing antibodies against HIV.

Abstract: IgM-multimerized single-domain antibodies that bind receptor tyrosine kinase (ROR1) are described. The IgM-multimerized single-domain antibodies can be used for multiple purposes including in research, imaging, diagnosis, and treatment of ROR1-related conditions and can be conjugated to form multi-domain binding molecules or antibody conjugates.

Abstract: The present disclosure provides compositions, kits, and methods to protect organs by inducing acquired cytoresistance without causing injury to the organ. The compositions, kits, and methods utilize heme proteins, iron and/or vitamin B12 and, optionally, agents that impact heme protein metabolism.

Abstract: Circular handed alpha-helical repeat proteins are described. The repeat proteins have a number of uses as scaffolds for geometrically precise, arrayed presentation of cell-signaling or immune-related protein and peptide epitopes, as well as numerous other therapeutic, diagnostic, and nanotechnological uses.

Abstract: The disclosure provides artificial nucleic acid introns configured for selective splicing in cells with aberrant RNA splicing activity, e.g., neoplastic cells. The artificial intron can comprise a 5? splice site, a canonical 3? splice site, at least one cryptic 3? splice site, a pyrimidine-rich domain, and at least one branchpoint. Also provided are constructs integrating the artificial introns with exons in a configuration that, when the artificial intron is spliced out by the aberrant RNA splicing factors, encode a functional protein. Also disclosed are methods that employ the disclosed platform of selective expression, including, targeted gene therapy methods (e.g., in cancers), diagnostics and imaging, and drug screening.

Abstract: Compositions and methods that rapidly and selectively modify hematopoietic stem cells (or cells derived therefrom) to achieve therapeutic objectives by providing for transient expression of nucleic acids are described. The transient expression leads to permanent therapeutic changes in the modified cells, referred to herein as “hit and run” effects.

Abstract: In various embodiments, the present disclosure provides chimeric antigen receptors (CARs) which bind to mesothelin. The mesothelin CARs comprise an extracellular region comprising a binding domain that specifically binds to at least a portion of mesothelin, a transmembrane region, and an intracellular region comprising an effector domain or a portion or variant thereof and a costimulatory domain or a portion or variant thereof. Recombinant host cells expressing the mesothelin CARs are also provided, as well as compositions and methods of treatment, prevention, and manufacture comprising the same.

Abstract: Disclosed herein are to markers, methods and systems for identifying cell populations, diagnosing, monitoring and treating cancer, including biomarkers predictive of response to immunotherapy treatment in Merkel cell carcinoma.

Abstract: A method of treating prostate cancer based on determining genome-wide methylation profile at a plurality of transcription factor binding sites in the total DNA obtained from cell-free biological samples from a subject suffering from prostate cancer are provided herein. Also described are methods for determining suitable treatment regimens for prostate cancer and methods for treating prostate cancer patients, based around selection of the patients according to the methods of the disclosure. The disclosure also relates to computer-implemented methods for identifying, diagnosing, staging, or otherwise characterizing cancers, in particular advanced prostate cancer. The methods of the present disclosure relate, inter alia, to isolating and analyzing the human DNA component from cell-free samples.

Abstract: The present disclosure relates to methods for using BCMA-specific binding molecules (such as a BCMA-specific chimeric antigen receptor or antibody) in combination with ?-secretase inhibitors, which can be done concurrently or sequentially, to treat or prevent a B-cell related proliferative disease, such as a cancer or autoimmune disease, or the like. A BCMA-specific binding molecule in combination with ?-secretase inhibitor can be used in, for example, adoptive immunotherapy.

Abstract: The disclosure provides compositions and related methods for detecting, inhibiting, reducing or killing tumor-infiltrating regulatory T cells (Tregs) characterized by expression of inducible T cell costimulator (ICOS) and Interleukin-1 receptor type 1 (IL-1R1). The reagents can include a bi-specific affinity reagent with a first domain that specifically binds ICOS and a second domain that specifically binds IL-1R1 or, separately, a first affinity reagent that specifically binds ICOS and a second affinity reagent that specifically binds IL-1R1. In some embodiments, the reagent can comprise engineered immune cells expressing a first chimeric antigen receptor (CAR) specific for ICOS and a second CAR specific for IL-1R1, wherein the cell requires binding by the first CAR and second CAR to activate, such as a logic-gated CAR T cell.