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: The present invention relates to methods and compositions for providing hematopoietic function to human patients in need thereof, by selecting a pool of expanded human cord blood stem/progenitor cell samples for administration to the patient, wherein the samples in the pool collectively do not mismatch the patient at more than 2 of the HLA antigens or alleles typed in the patient; and administering the selected pool of expanded human cord blood stem/progenitor cell samples to the patient. Methods for obtaining the pools of expanded human cord blood stem/progenitor cell samples, banks of frozen pools of expanded human umbilical cord blood stem/progenitor cell samples, and methods for producing such banks are also provided herein.

Abstract: The present disclosure relates to 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. The present disclosure also relates to uses of immune cells expressing such immunomodulatory fusion proteins to treat certain diseases, such as cancer or infectious disease.

Abstract: The present disclosure provides reagents and methods for treating disease using modified immune cells (e.g., T cell comprising CAR or TCR) in combination with an agent associated with induction of immunogenic cell death (ICD) and optionally further in combination with an agent that specifically binds to and/or inhibits an immune suppression component and/or an agonist of an immune stimulatory molecule.

Abstract: Engineered trimeric CD70 proteins for use in ex vivo T cell manufacturing are described. Use of the proteins during manufacturing creates expanded T cell populations with enhanced properties such as earlier proliferation in culture; selective expansion of nave and memory T cell subsets; longer persistence in vivo following administration to a subject; and improved therapeutic effect. Use of the proteins as therapeutics provide anti-cancer and anti-viral effects. The proteins can also be used as agonistic cell culture reagents in in vitro uses.

Abstract: Methods and kits to distinguish normal or Barrett's esophageal samples from high grade dysplasia (HGD), esophageal adenocarcinoma (EAC), or junctional adenocarcinoma (JCA) samples are described. The methods and kits utilize the methylation status of epigenetic markers, such as cg6522, POU3F1, YPEL3, and/or MAFB.

Abstract: Small cell lung cancer specific chimeric antigen receptor comprising: an antigen-binding domain capable of specifically binding an antigen selected from Tables 1A, 1B, 2A, 2B and 4 and/or that specifically binds to or interacts GAD65, PTPRU, TFRC and GABA-b. A method for treating a subject suffering from SCLC comprising, introducing into the subject a therapeutically effective amount of a T lymphocyte comprising a chimeric antigen receptor. An antigen binding molecule, comprising: an antigen-binding domain capable of specifically binding an antigen selected from Tables 1A, 1B, 2A, 2B and 4 and/or that specifically binds to or interacts GAD65, PTPRU, TFRC and GABA-b. A method of detecting an SCLC tumor in a subject.

Abstract: Provided are adoptive cell therapy methods involving the administration of doses of cells for treating B cell malignancies. The cells generally express recombinant receptors such as chimeric antigen receptors (CARs). In some embodiments, the methods are for treating subjects with chronic lymphocytic leukemia (CLL). In some embodiments, the methods are for treating subjects with non-Hodgkin lymphoma (NHL). In some embodiments, the methods involve prior administration of a lymphodepleting therapy, such as prior administration of fludaribine and/or another lymphodepleting chemotherapeutic agent, for example cyclophosphamide. In some embodiments, features of the methods include an increase in complete remission, overall survival and/or progression free survival of subjects treated in accord with the provided methods.

Abstract: The present disclosure provides compositions and methods that rapidly and selectively modify cells of the immune system to achieve therapeutic objectives. The methods can be practiced in vivo and any cell type that expresses a known marker can be targeted for a therapeutic objective.

Abstract: Systems and methods for modeling highly complex biological relations in machine-learned models, such as neural networks (e.g., such as deep neural networks (DNNs)), to predict biological outcomes and elucidate underlying mechanisms are described. The systems and methods utilize recursive feature elimination and scoring and can be utilized to prioritize particular compounds or treatments for clinical development and direct new avenues of research and development based on elucidated mechanisms.

Abstract: The present disclosure provides compositions and methods for targeting a neoantigen to, for example, treat or prevent cancer. Disclosed embodiments include binding proteins, such as T cell receptors bind to a neoantigen:HLA complex. Disclosed binding proteins are highly sensitive to antigen, capable of inducing activation of host T cells at low concentrations of peptide antigen. In certain embodiments, binding proteins of the present disclosure are non-alloreactive against, are substantially non-alloreactive against, and/or have a low risk of alloreactivity against (i) amino acid sequences from the human proteome and/or (ii) against human HLA alleles. 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.

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: Chimeric antigen receptor (CAR) with a binding domain that binds STEAP1 are disclosed. The CAR disclosed herein can be used in the treatment of prostate cancer, the Ewing family of tumors (EFT), bladder cancer, ovarian cancer, and rhabdomyosarcoma. The CAR disclosed herein can bind and elicit cytotoxic effects even in low antigen density conditions.

Abstract: Newborn screening for primary immunodeficiencies, cystinosis, and Wilson disease is described. The newborn screening can detect these disorders from dried blood spots already routinely collected at the time of birth. Early detection of these disorders will greatly improve patient outcome as each of them can be fatal once symptoms emerge.

Abstract: DNA hypomethylation as a predictive marker for cancer therapy is described. The susceptibility of hypomethylated cancers to particular treatments, for example to AKT inhibitors and anthracyclines is described. The described susceptibilities can be used to direct enrollment of subjects into appropriate clinical trials and to guide treatment selection and administration based on global DNA methylation level.

Abstract: Siderocalin-metal chelator combinations that bind metallic radioisotopes used in nuclear medicine with high affinity are described. The high affinity siderocalin-metal chelator combinations include a number of chelator backbone arrangements with functional groups that coordinate with metals. The siderocalin-metal chelator combinations can be used to deliver radionuclides for imaging and therapeutic purposes.

Abstract: Provided herein are combination therapies involving administration of an immunotherapy involving a cell therapy, such as a T cell therapy, and an inhibitor of gamma secretase. Also provided are methods for engineering, preparing, and producing the cells, compositions containing the cells and/or gamma secretase inhibitor, and kits and devices containing and for using, producing and administering the cells and/or gamma secretase inhibitor, such as in accord with the provided combination therapy methods.

Abstract: A method for analyzing an ability of target nucleic acid sequences to impact gene expression is described. In an embodiment, the method includes cloning the target nucleic acid sequences and associated barcode nucleic acid sequences into a plurality of plasmids, sequencing the plasmids to provide long-read sequencing information based on a target nucleic acid sequence of the target nucleic acid sequences and an associated barcode nucleic acid sequence, associating the target nucleic acid sequence with the associated barcode nucleic acid sequence based on the long-read sequencing information, transducing the plurality of plasmids into a plurality of cells, extracting DNA, total mRNA, and polysome-bound mRNA from the cells, sequencing the barcode nucleic acid sequences in the extracted DNA, total mRNA, and polysome-bound mRNA to provide short-read sequencing information, and analyzing the target nucleic acid sequences by comparing the long-read sequencing information and the short-read sequencing information.

Abstract: Provided herein are methods and compositions for overcoming resistance to and/or augmenting efficacy of Prostate specific membrane antigen (PSMA)-directed therapies in a subject. In some embodiments, the method comprises administering to the subject in need thereof an effective amount of at least one agent capable of modulating the expression of PSMA. The disclosure also is directed to a method for sensitizing a cancer to a PSMA-targeted therapeutic agent and/or a PSMA-targeted theranostic agent in a subject in need thereof. Also provided are methods and compositions for treating prostate cancer in a subject in need thereof.