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: 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: Antibodies that bind the tumor (T) antigen of the Merkel cell polyomavirus are disclosed. The antibodies can be use used in cell-based immunotherapies, antibody-based therapies, diagnostics, and detection assays, among other uses.

Abstract: In various embodiments, provided are immune response signatures that can be used for the diagnosis, monitoring, and treatment of long-term diseases and inflammatory disorders caused by viral infections. In some embodiments, the viral infection is SARS-CoV-2 infection. In some embodiments, the long-term disease is post-acute sequelae of SARS-CoV-2 infection (PASC).

Abstract: The present invention relates to the use of halogen compounds, including iodide, and chalcogenide compounds, including iodide, sulfide and selenide, to treat and prevent diseases and injuries. The present invention further relates to compositions comprising a halogen compound and/or a chalcogenide compound, including pharmaceutical compositions, as well as methods of manufacturing such compounds and administering such compositions to subjects in need thereof.

Abstract: The present invention features modified polynucleotide sequences that mimic host cell DNA and methods of using such sequences for the genetic engineering of bacteria that are otherwise genetically intractable.

Abstract: Described herein are immunomodulatory fusion proteins containing an extracellular binding domain and an intracellular signaling domain, wherein binding of a target can generate a modulatory signal in a host cell, such as a T cell. Some immunomodulatory fusion proteins as described comprise a SIRP? extracellular component and hydrophobic and intracellular components comprising transmembrane and/or signaling domains of a CD28, respectively. Such fusion proteins are capable of delivering a positive or costimulatory signal in response to a binding event that in a natural setting would result in an inhibitory signal. Uses of immune cells expressing such immunomodulatory fusion proteins to treat certain diseases, such as cancer or infectious disease, are also described.

Abstract: Methods to create chemically-induced dimerizing (CID) protein systems and uses thereof are described. The methods utilize antibody binding domain dimerizing proteins. The created systems can be used to regulate cellular events such as gene expression, receptor signaling and cell death to effectuate a variety of clinically relevant treatment outcomes.

Abstract: The present disclosure relates to tagged chimeric effector molecules and receptor molecules thereof for genetically engineering a host cell, wherein the recombinant host cell can be identified, isolated, sorted, induced to proliferate, tracked or eliminated. For example, a T cell may be recombinantly modified for use in adoptive immunotherapy.

Abstract: Mesothelin (MSLN) is expressed on pancreatic cancers, ovarian cancers and mesotheliomas. The present disclosure provides antigen-binding molecules, including anti-MSLN antibodies, and bispecific antigen-binding molecules that bind to both MSLN and a T cell antigen (e.g., CD3) and activate T cells in the presence of MSLN-expressing tumor cells. The antigen-binding molecules of this disclosure are useful for the treatment of diseases and disorders in which a MSLN-targeted immune response is desired and/or therapeutically beneficial. For example, the antigen-binding molecules of the present disclosure are useful for the treatment of various cancers, including pancreatic cancer, ovarian cancer and mesotheliomas.

Abstract: Antibodies that protect against respiratory viral infections including human parainfluenza viruses (HPIV), respiratory syncytial virus (RSV), and human metapneumovirus (HMPV) are described. Certain antibodies disclosed herein neutralize more than one virus (e.g., RSV and HMPV). The binding fragments of the antibodies can be engineered into numerous formats including those that provide simultaneous protection against multiple viruses.

Abstract: The present disclosure provides compositions and methods for improved pre-targeted radioimmunotherapeutics (PRIT) to treat various hematological disorders, such as B cell hyperproliferative disorders and solid tumors. The disclosed compositions include bispecific antibody compositions having a first domain that specifically bind to an antigen such as CD38, BCMA, Muc1, GPRC5D, or Slam7, and a second domain that specifically binds to a radioactive ligand. Methods include administering the disclosed bispecific antibody reagent and separately administering the radioactive ligand. In some embodiments, a clearing agent is also administered. In some embodiments, the therapeutic methods comprise administering a combination of two or more bispecific antibody reagents. In some embodiments, an enhancing agent, such as ATRA, gamma secretase inhibitor, or dextramethasone, is also administered to enhance expression of the target antigen on the target cells.

Abstract: Antibodies that bind the tumor (T) antigen of the Merkel cell polyomavirus are disclosed. The antibodies can be use used in cell-based immunotherapies, antibody-based therapies, diagnostics, and detection assays, among other uses.

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: 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 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.