Abstract: Methods for treating malignancies such as hematological malignancies, including myeloma, that are resistant to tissue transplant treatments and that can be characterized by an increased risk of relapse or graft-versus-host disease (GVHD). A method for treatment includes transplanting a tissue that includes T cells to a subject, enriching for a stem-like memory T cell phenotype in the T cells, and stimulating the T cells to enhance a graft-versus-tumor (GVT) response of the T cells. The enriching for the stem-like memory T cell phenotype can include depletion of exhausted alloreactive T cells with a post-transplant cyclophosphamide (PT-Cy) treatment and the stimulating the T cells can include an agonist immunotherapy, such as a decoy-resistant IL-18 (DR-18) treatment, to enhance the GVT response.

Abstract: The disclosure provides methods of enhancing susceptibility of neoplastic, transformed, and/or cancer cells (“cancer cells”) to immunotherapeutic agents. The methods comprise contacting the cancer cell with an agent that modulates RNA splicing. In some embodiments, the method further comprise contacting the cancer cell with the immunotherapeutic agent, such as an immune checkpoint inhibitor. The disclosure also provides compositions and/or methods for treating a subject with cancer. In some embodiments, the disclosure provides compositions and methods for combination therapy that comprises administering to a subject with cancer an effective amount of an agent that modulates RNA splicing and a therapeutically effective amount of an immunotherapeutic agent, such as an immune checkpoint inhibitor.

Abstract: A suite of novel anti-CD33 antibodies is described. The provided antibodies are pan-binders, binding the C2-set Ig-like domain in the presence or absence of the V-set Ig-like domain of CD33; are C2-set specific binders, binding the C2-set Ig-like domain only in the absence of the V-set Ig-like domain of CD33; or are V-set binders, binding the V-set Ig-like domain of CD33. The antibodies provide novel therapeutic and diagnostic tools against CD33-related disorders, such as acute myeloid leukemia (AML).

Abstract: Strategies to assess and/or produce cell populations with predictive engraftment potential are described. The cell populations can be used for a variety of therapeutic and research purposes.

Abstract: Chimeric antigen receptors (CARs) with binding domains derived from a novel suite of CD33-binding antibodies are described. The CARs include optimized short and intermediate spacer regions. The current disclosure also provides methods of cell expansion/activation processes utilizing IL-2, IL-7, IL-15, and/or IL-21 that improve cellular proliferation and cell lysis of the CARs as described.

Abstract: Peptides that home, target, migrate to, are directed to, are retained by, or accumulate in and/or binds to the cartilage of a subject are disclosed. Pharmaceutical compositions and uses for peptides or peptide-active agent complexes comprising such peptides are also disclosed. Such compositions can be formulated for targeted delivery of a drug to a target region, tissue, structure or cell in the cartilage. Targeted compositions of the disclosure can deliver peptide or peptide-active agent complexes to target regions, tissues, structures or cells targeted by the peptide.

Abstract: A suite of novel human anti-CD33 antibodies is described. The provided antibodies are pan-binders, binding the C2-set Ig-like domain in the presence or absence of the V-set Ig-like domain of CD33 or are V-set binders, binding the V-set Ig-like domain of CD33. The antibodies provide novel therapeutic and diagnostic tools against CD33-related disorders, such as acute myeloid leukemia (AML).

Abstract: The present disclosure provides, among other things, immune suppression regimens for in vivo gene therapy and uses thereof. In various embodiments of the present disclosure, in vivo gene therapy includes delivery of at least one exogenous coding nucleic acid sequence to a stem cell of the subject. Success of in vivo gene therapy can be inhibited or reduced by immunotoxicity. The present disclosure provides compositions and methods, including among other things immune suppression regimens, that reduce immunotoxicity of in vivo gene therapy, e.g., in vivo gene therapy including administration of a viral gene therapy vector to a subject.

Abstract: In some aspects, the disclosure provides antibody-based reagents that specifically bind a tropomyosin receptor kinase B (TrkB) isoform that is associated with cancers. In some embodiments, the isoform is TrkB.T1. In some embodiments, the antibody or antibody derivative specifically binds a polypeptide comprising, consisting essentially of, or consisting of the sequence FVLFHKIPLDG (SEQ ID NO:1), or a sequence with at least 80% sequence identity thereto. In other aspects, the disclosure provides methods of producing the antibody or antibody derivative, related hybridomas, and methods of detecting and treating cancers incorporating use of the disclosed antibody reagents.

Abstract: Genomic safe harbors (GSH) for genetic therapies in human stem cells and engineered nanoparticles to provide targeted genetic therapies are described. The GSH and/or associated nanoparticles can be used to safely and efficiently treat a variety of genetic, infectious, and malignant diseases.

Abstract: Systems and methods to genetically modify B cells to express selected antibodies are described. The systems and methods can be used to: obviate the need for classical vaccinations; provide protection against infectious agents for which no vaccinations are currently available; provide protection against infectious agents when patients are otherwise immune-suppressed; and/or provide a benefit provided by a therapeutic antibody, such as in the treatment of autoimmune disorders.

Abstract: Systems and methods to increase the efficacy of vaccines that require or are rendered more effective with T cell mediated immunity are described. The systems and methods utilize polynucleotides that genetically modify T cells to express a T cell receptor specific for an administered vaccine antigen.

Abstract: Described herein are peptides and variants and mutants thereof capable of interacting with TEAD, disrupting the HIPPO pathway, or modulating the activity or function of TEAD interactions in a cell. Pharmaceutical compositions and uses of peptides, as well as methods of designing and manufacturing such peptides, to treat cancer, tumor, or any other disease/condition associated with a dysregulated HIPPO pathway or uncontrolled cell growth are also described herein.

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 present disclosure provides binding proteins and TCRs with high affinity and specificity against Merkel cell polyomavirus T antigen epitopes or peptides, T cells expressing such high affinity Merkel cell polyomavirus T antigen specific TCRs, nucleic acids encoding the same, and compositions for use in treating Merkel cell carcinoma.

Abstract: Systems and methods to selectively protect therapeutic cells by reducing CD33 expression in the therapeutic cells using base editors and targeting non-therapeutic cells with an anti-CD33 therapy are described. The selective protection results in the enrichment of the therapeutic cells while simultaneously targeting any diseased, malignant and/or non-therapeutic CD33 expressing cells within a subject.

Abstract: The present disclosure provides compositions and methods for targeting a Ras antigen to, for example, treat or prevent cancer. Disclosed embodiments include binding proteins, such as a T cell receptor or a chimeric antigen receptor, that bind to a Ras antigen:HLA complex. Polynucleotides encoding such binding protein can introduced into a host cell, such as a T cell, and the cell can be used in immunotherapy for treating various cancers. Also provided are immunogenic polypeptides that can be useful to, for example, induce an immune response against a mutated Ras or to identify a binding protein that binds to a Ras antigen.

Abstract: Systems and methods to increase the efficacy of vaccines that require or are rendered more effective with T cell mediated immunity are described. The systems and methods utilize polynucleotides that genetically modify T cells to express a T cell receptor specific for an administered vaccine antigen.

Abstract: The present invention relates to methods, kits and compositions for expansion of embryonic hematopoietic stem cells and providing hematopoietic function to human patients in need thereof. In one aspect, it relates to kits and compositions comprising a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TGF? pathway. Also provided herein are methods for expanding embryonic hematopoietic stem cells using kits and compositions comprising a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TGF? pathway. The embryonic hematopoietic stem cells expanded using the disclosed kits, compositions and methods include cells derived from an embryo (e.g., aorta-gonad-mesonephros region of the embryo), embryonic stem cells, induced pluripotent stem cells, or reprogrammed cells of other types.

Abstract: The present disclosure provides compositions and methods for accurately detecting mutations by uniquely tagging double stranded nucleic acid molecules with dual cyphers such that sequence data obtained from a sense strand can be linked to sequence data obtained from an anti-sense strand when sequenced, for example, by massively parallel sequencing methods.