Abstract: Activity-inducible fusion proteins whose activity is post-translationally regulated utilizing a hsp90 binding domain and a drug molecule are described. In the absence of the drug molecule, the activity-inducible fusion proteins are inactivated but can be activated by a relevant physiological parameter in the presence of the drug molecule. Examples of the activity-inducible fusion proteins include chimeric antigen receptors (CAR) wherein the relevant physiological parameter is antigen binding.

Abstract: The present disclosure provides improved compositions for the homology directed repair of the human globin locus for the prevention, treatment, or amelioration of at least one symptom of a hemoglobinopathy.

Abstract: A CD19-OR-CD20 chimeric antigen receptor (CAR) protein construct is provided. Also provided are nucleic acids encoding the CD19-OR-CD20 CAR; and methods of use, e.g. in the treatment of B cell malignancies. The CD19-OR-CD20 CAR of the invention is a bispecific CAR that can trigger T-cell activation upon detection of either CD19 or CD20 (or both). It is a single molecule that confers two-input recognition capability upon human T cells engineered to stably express this CAR.

Abstract: The present disclosure relates to the co-expression of an endonuclease with an end-processing enzyme for the purpose of enhanced processing of the polynucleotide ends generated by endonuclease cleavage.

Abstract: Early detection of lysosomal storage diseases (LSDs) including Mucopolysaccharidosis Type I (MPS I) and Pompe Disease can greatly improve patient outcome as each disease can be fatal once symptoms emerge. Screening for MPS I and Pompe Disease using biological samples including dried blood spots (DBS), buccal swab, peripheral blood mononuclear cells (PBMCs), or white blood cells (WBCs) is described. The disclosed methods and assays provide a robust way to screen newborns for LSDs. The disclosed methods and assays can also allow rapid prediction of whether a patient with LSD will develop an immune response to enzyme replacement therapy (ERT), thus improving treatment for patients with LSDs. The disclosed methods and assays can also further reduce the number of false positives caused by pseudo deficiency cases of LSD, such as MPS I and Pompe Disease.

Abstract: The present application relates to plasma cells and plasma cell precursors that express a macromolecule, such as a protein, protein mimetic or a peptide and compositions comprising these plasma cells or plasma cell precursors. The application further relates to methods of using and making the plasma cells and plasma cell precursors that express the macromolecule. Methods of treatment comprising administering the plasma cells or plasma cell precursors are also contemplated.

Abstract: Aspects of the invention described herein relate to methods of making and using inducible promoters for transgene expression. The inducible promoters are derived from the NFAT-RE inducible system and are used to improve or enhance T cell survival and proliferation.

Abstract: In Hybrid and truncated immune cell proteins are described. Hybrid proteins are stimulatory and include an extracellular domain of one stimulatory immune cell protein, an intracellular domain of a different stimulatory immune cell protein, and a transmembrane domain linking the extracellular domain to the intracellular domain. Truncated proteins include an immune cell receptor ligand and a transmembrane domain but lack a functional intracellular domain. The hybrid and truncated proteins can be used to modulate and/or diversify immune cell activation in the fight against cancers and infectious diseases, among other uses.

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: The present disclosure relates to biomarker profiles and their use to predict a subject's response to an immunomodulatory treatment. Biomarkers in these profiles include cytokines and other proteins associated with the interleukin 1 family and the type 1 interferon family. Particular biomarkers include interleukin (IL)-2, soluble IL-2 receptor alpha (sIL-2RA), IL-5, IL-6, IL-9, IL-10, IL-18, IL-18 binding protein (IL-18BP), IL-18 receptor 1 (IL-18R1), IL-18 receptor accessory protein (IL-18RAP), IL-22, C-type lectin-like receptor (CD161), CD56, interferon gamma (IFN?), granulocyte macrophage colony stimulating factor (GM-CSF), serum amyloid A (SAA), and C-reactive protein (CRP). Particular biomarkers also include populations of cells including CD161+ cells and CD56+dim cells. The biomarker profiles can be used to predict a subject's responsiveness to an immunomodulatory treatment (e.g.

Abstract: A method for determining a presence of arthritis in a patient, including obtaining a first image of a patient's joint, wherein the first image is a visible light image, obtaining a second image of the patient's joint, wherein the second image is a thermal light image, determining an outline of the patient's joint from the first image, determining an outline of a reference area from the first image, wherein the patient's joint is adjacent to the reference area, determining a first representative topological temperature within the outline of the patient's joint of the first image from the second image, determining a second representative topological temperature within the outline of the reference area of the first image from the second image, comparing the first representative topological temperature and the second representative topological temperature; and determining a likelihood of the presence of arthritis within the patient's joint.

Abstract: Disclosed herein are methods of treatment of autoimmune diseases such as systemic lupus erythematosus (SLE) as well as clinical assays for detection of autoimmune disease activity in patients utilizing a PD1 ligand.

Abstract: Aspects of the invention described herein relate to methods of making and using inducible promoters for transgene expression. The inducible promoters are derived from the NFAT-RE inducible system and are used to improve or enhance T cell survival and proliferation.

Abstract: The disclosure provides immunogenic peptides comprising at least a portion of a Plasmodium HAP2 paralog (“HAP2p”) protein, immunogenic compositions comprising or encoding the immunogenic peptides, antibodies binding the immunogenic peptides, and methods of preventing Plasmodium transmission incorporating the peptides, compositions, and/or antibodies. In some embodiments, the immunogenic peptide has a sequence comprising a sequence with at least 80% identity to a sequence of at least 10 continuous amino acids of SEQ ID NO:2, a Plasmodium HAP2 paralog (“HAP2p”) protein.

Abstract: Disclosed are methods of making a genetically modified immune cell for modifying a tumor microenvironment (TME) and methods of modifying a tumor microenvironment (TME). In some embodiments, the method can include delivering a first vector to an immune cell, wherein the first vector comprises a nucleic acid encoding a protein that induces T-cell proliferation, promotes persistence and activation of endogenous or adoptively transferred NK or T cells and/or induces production of an interleukin, an interferon, a PD-1 checkpoint binding protein, HMGB1, MyD88, a cytokine or a chemokine. Methods of modulating the suppression of the immune response in a tumor microenvironment, minimizing the proliferation of tumor and suppressive cells, and increasing the efficiency of an anti-cancer therapy, anti-infection therapy, antibacterial therapy, anti-viral therapy, or anti-tumoral therapy are also provided.

Abstract: The current disclosure provides chimeric antigen receptors (CARs) that bind a natural killer (NK) cell surface marker, resulting in destruction of the bound NK cell. The NK cell surface markers include an activating NK cell receptor, and an inhibitory NK cell receptor. Cells that are genetically modified to express these CARs and uses of the CAR modified cells are also described.

Abstract: Single-domain antibodies that bind the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) spike protein are disclosed. The single-domain antibodies include binding domains that bind epitopes of the Spike ectodomain inside and outside the receptor binding domain. The single-domain antibodies can be used for multiple purposes including in the research, diagnosis, and prophylactic or therapeutic treatment of COVID-19.

Abstract: The use of inhibitors upstream of mTOR in the CSF1 pathway of neuroinflammation, inhibitors of chemokine receptor CXCR3, functional derivatives thereof, and/or immunosuppressant drugs to reduce neuroinflammation are disclosed. The inhibitors and/or immunosuppressant drugs can treat genetic or environmental encephalopathies and/or reduce microglial activation. Treated encephalopathies include Leigh Syndrome and Wernicke encephalopathy.

Abstract: The present disclosure relates to methods of treating a patient with a cancer by administering to the patient a composition comprising CAR T cells wherein the CAR T cells comprise a CAR and the CAR comprises an E2 anti-fluorescein antibody fragment, and administering to the patient a small molecule linked to a targeting moiety by a linker. The disclosure also relates to compositions for use in such methods.

Abstract: Provided are methods for preventing or ameliorating toxicity caused by or due to a therapy, such as an immunotherapy or a cell therapy, by pre-emptive or early administration toxicity-targeting agent(s). In some embodiments, the therapy is a cell therapy in which the cells generally express recombinant receptors such as chimeric receptors, e.g., chimeric antigen receptors (CARs) or other transgenic receptors such as T cell receptors (TCRs). Features of the methods, including the timing of the administration of the agents or treatments for toxicity, provide various advantages, such as lower toxicity while maintaining persistence and efficacy of the administered cells.