Abstract: The present disclosure provides methods for generating enhanced affinity T cell receptors by agonist selection of hematopoietic progenitor cells expressing an antigen specific TCR? cultured with stromal cells expressing Delta-like-1 or Delta-like-4, compositions prepared from such methods, and uses of thereof.

Abstract: Abstract of the Disclosure Disclosed herein are methods and compounds for screening and identifying ligands of G protein-coupled receptors (GPCRs). Also disclosed are chimeric G proteins and methods for detecting the activation or inhibition of GPCRs.

Abstract: The invention provides HSV antigens that are useful for the prevention and treatment of HSV infection, including epitopes confirmed to be recognized by T-cells derived from herpetic lesions. T-cells having specificity for antigens of the invention have demonstrated cytotoxic activity against cells loaded with virally-encoded peptide epitopes, and in many cases, against cells infected with HSV. The identification of immunogenic antigens responsible for T-cell specificity provides improved anti-viral therapeutic and prophylactic strategies. Compositions containing antigens or polynucleotides encoding antigens of the invention provide effectively targeted vaccines for prevention and treatment of HSV infection.

Abstract: Disclosed herein are compounds, and pharmaceutical compositions that include such compounds, for preventing or treating hearing loss. The compounds and pharmaceutical compositions described herein prevent or treat hair cell death. In addition, the compounds and pharmaceutical compositions described herein protect against kidney damage in an individual receiving an aminoglycoside antibiotic. Methods of using the compounds, alone or in combination with other therapeutic agents, are also disclosed.

Abstract: A method of carrying out adoptive immunotherapy by administering a subject an antigen-specific cytotoxic T lymphocytes (CTL) preparation in a treatment-effective amount is described. In the method, the CTL preparation is preferably administered as a preparation of an in vitro antigen-stimulated and expanded primate CTL population, the CTL population: (i) depleted of FoxP3+ T lymphocytes prior to antigen stimulation; (ii) antigen-stimulated in vitro in the presence of interleukin-21; or (iii) both depleted of FoxP3+ T lymphocytes prior to antigen stimulation and then antigen-stimulated in vitro in the presence of interleukin-21. Methods of preparing such compositions, and compositions useful for carrying out the adoptive immunotherapy, are also described.

Abstract: The present invention provides methods for treating cancers having a mutation in one or more tumor suppressor genes, comprising providing to a subject in need thereof an inhibitor of a kinase, as well as related methods and compositions.

Abstract: Described herein are methods for treating hematological malignancies and/or solid tumors in a subject using inhibitors of integrin alpha 6. In some embodiments, the inhibitors are monoclonal antibodies. The antibodies may be conjugated to additional therapeutic agents. The antibodies may be co-administered sequentially or simultaneously with additional therapeutic agents.

Abstract: Disclosed herein are compounds, and pharmaceutical compositions that include such compounds, for preventing, treating, and/or protecting against sensory hair cell death. Methods of using the compounds, alone or in combination with other therapeutic agents, are also disclosed.

Abstract: The present invention provides nanoparticles having a core comprising a magnetic material and having a surface, where the surface may be operatively linked to an antigenic peptide-major histocompatibility complex (MHC) monomer. The antigenic peptide-MHC monomer may then be recognized by a T cell receptor. These nanoparticles may further comprise a signal-generating label, such as a fluorophore. Methods employing nanoparticles of the present invention may involve magnetic resonance imaging and/or fluorescence detection, such that cell imaging and localization are performed.

Abstract: In one aspect, the present invention provides an intron-modified capsid expression cassette useful for generating adeno-associated virus (AAV) vector particles. In another aspect, the present invention provides a method of reducing the immune response in a mammalian subject undergoing treatment with an AAV vector.

Abstract: In one embodiment, a gene expression signature for predicting risk of developing therapy-related myelodysplasia or acute myeloid leukemia (t-MDS/AML) after autologous hematopoietic cell transplantation (aHCT) is provided. In another embodiment, a method for predicting a risk for development of t-MDS/AML after aHCT is provided. Such a method may include providing a biological sample that contains CD34 cells from a subject; detecting a test expression level of a set of two or more genes of a gene expression signature; comparing the test expression level of a set of corresponding training expression levels that include a training case expression level and a training control expression level; and predicting a high risk of developing t-MDS/AML when the test expression level is at or about the training case expression level or predicting a low risk of developing t-MDS/AML when the test expression level is at or about the training control expression level.

Abstract: Compositions and methods are described for highly sensitive quantification of the relative representation of DNA from adaptive immune cells (e.g., T and/or B lymphocytes) in DNA extracted from complex mixtures of cells that include cells which are not adaptive immune cells. Included are methods for determining the relative presence in a tumor of tumor infiltrating lymphocytes (TIL), the relative presence of lymphocytes infiltrating a somatic tissue that is the target of an autoimmune disease, and the relative presence of lymphocytes infiltrating a transplanted organ.

Abstract: The invention generally relates to methods for identifying and using anticancer therapeutic agents and, more particularly, to methods for identifying and using inhibitors of genes for inhibiting the growth and/or proliferation of MYC-driven tumor cells relative to normal cells.

Abstract: A synthetic polypeptide vaccine is employed for directed targeting of an individual's immune response to an antigen of interest. The synthetic polypeptide contains a carrier epitope specific for open conformers of an individual's MHC-I molecules in the presence of HLA-F, and also contains an effector epitope which elicits an immune response to the antigen of interest. The effect- or epitope may modulates an immune response to a tumor, pathogen, or autoantigen associated with an autoimmune disorder. The present vaccine exploits a role for the interaction between HLA-F and open conformers of MHC-I in the uptake of extracellular antigen for cross presentation.

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 compositions and methods for treating or reducing the risk of pancreatic cancer by administering compounds capable of inhibiting the expression or activity of RUNX3.

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 TGFp 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 TOP? 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 invention provides an optimized FLP site-specific recombinase coding sequence and methods for its use. This genetically engineered FLP gene displays a marked increase in recombination efficiency compared to the native FLP gene and is therefore useful in a wide array of molecular applications.

Abstract: A fluid delivery device includes an array of needles, each in fluid communication with a respective reservoir. Respective actuators are coupled so as to be operable to drive fluid from the reservoirs via needle ports. Each needle can have a plurality of ports, and the ports can be arranged to deliver a substantially equal amount of fluid at any given location along its length. A driver is coupled to the actuators to selectively control the rate, volume, and direction of flow of fluid through the needles. The device can simultaneously deliver a plurality of fluid agents along respective axes in solid tissue in vivo. If thereafter resected, the tissue can be sectioned for evaluation of an effect of each agent on the tissue, and based on the evaluation, candidate agents selected or deselected for clinical trials or therapy, and subjects selected or deselected for clinical trials or therapeutic treatment.

Abstract: A fluid delivery device includes an array of needles, each in fluid communication with a respective reservoir. Respective actuators are coupled so as to be operable to drive fluid from the reservoirs via needle ports. Each needle can have a plurality of ports, and the ports can be arranged to deliver a substantially equal amount of fluid at any given location along its length. A driver is coupled to the actuators to selectively control the rate, volume, and direction of flow of fluid through the needles. The device can simultaneously deliver a plurality of fluid agents along respective axes in solid tissue in vivo. If thereafter resected, the tissue can be sectioned for evaluation of an effect of each agent on the tissue, and based on the evaluation, candidate agents selected or deselected for clinical trials or therapy, and subjects selected or deselected for clinical trials or therapeutic treatment.