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: 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: Chimeric antigen receptors (CAR) that bind Preferentially Expressed Antigen in Melanoma (PRAME) ALY(SEQ ID NO: 94)/HLA-A2 are disclosed. The CAR can be used to treat PRAME/HLA-A2 expressing cancers such as the t(8;21), Inv(16), and KMT2A-r forms of acute myeloid leukemia (AML).

Abstract: Single-domain antibodies that bind receptor tyrosine kinase (ROR1) are described. The single-domain antibodies can be used for multiple purposes including in research, imaging, diagnosis, and treatment of ROR1-related conditions. The disclosed single-domain antibodies can be used as anti-cancer therapeutics such as antibody-drug conjugates, multi-domain binding molecules, or recombinant receptors or can be used as cancer imaging/diagnostic agents.

Abstract: The use of luteinizing hormone receptor (LHR) binding agents and luteinizing hormone (LH) agonists to enrich for primitive hematopoietic stem cell (pHSC) populations, to target pHSC for ablation, and/or to expand pHSC populations are described. The methods can be used to prepare therapeutic hematopoietic stem cell (HSC) populations, to prepare patients for therapeutic HSC transplants, and/or to treat malignancies, such as those associated with hyperproliferative HSC.

Abstract: Anti-Epstein Barr Virus (EBV) vaccines are described herein. The EBV vaccine antigens are linked to a multimerization domain, for example, presented on a circular tandem repeat protein (cTRP) scaffold or linked to a C4b multimerization domain. The vaccines can be used to treat and/or reduce the risk of EBV infection and to treat and/or reduce the risk of complications associated with EBV infection, such as infectious mononucleosis, lymphoproliferative disorders, carcinomas, and smooth muscle tumors.

Abstract: Delta-like non-canonical Notch ligand 1 (DLK1) inhibitors are disclosed. The DLK1 inhibitors can be used to treat cancers such as myelodysplastic syndrome (MDS), and cancers of the liver, breast, brain, pancreas, colon, lung, kidney, ovary, testes, and/or adrenal gland, among other uses described herein.

Abstract: The present disclosure relates to anti-ROR1 binding proteins, including those that bind to a ROR1 or portion thereof such as an intracellular C terminal portion of a ROR1 protein, and the use of such binding proteins in immunohistochemical and diagnostic methods. Related kits and methods of using the binding proteins are also provided, as are methods of treatment of subjects having diseases or conditions determined to be candidates for such treatments by the binding proteins or methods of this disclosure.

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: A method of measuring immunocompetence is described. This method provides a means for assessing the effects of diseases or conditions that compromise the immune system and of therapies aimed to reconstitute it. This method is based on quantifying T-cell diversity by calculating the number of diverse T-cell receptor (TCR) beta chain variable regions from blood cells.

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: 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: 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: 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: 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: 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: 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.