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: Methods are provided for predicting a subject's infection status using high-throughput T cell receptor sequencing to match the subject's TCR repertoire to a known set of disease-associated T cell receptor sequences. The methods of the present invention may be used to predict the status of several infectious agents in a single sample from a subject. Methods are also provided for predicting a subject's HLA status using high-throughput immune receptor sequencing.

Abstract: Methods are provided for identifying T cell receptors that specifically bind a particular antigenic target and can be used as therapeutics against disease.

Abstract: The present disclosure provides TCRs with high or enhanced affinity against various tumor associated antigens (including human MAGE-A1 epitopes), T cells expressing such high affinity antigen-specific TCRs, nucleic acids encoding the same, and compositions for use in treating diseases or disorders in which cells overexpress one or more of these antigens, such as in cancer.

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: 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: The present disclosure provides TCRs with high or enhanced affinity against various tumor associated antigens (including human Wilms tumor protein 1 (WT 1) epitopes and mesothelin epitopes), T cells expressing such high affinity antigen specific TCRs, nucleic acids encoding the same, and compositions for use in treating diseases or disorders in which cells overexpress one or more of these antigens, such as in cancer.

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: Treatment protocols based on expression of therapeutic proteins by genetically-modified selected cell types in vivo are described. The treatment protocols can additionally utilize cell attractants to attract selected cell types to a treatment site and/or macrophage activation protocols at the treatment site.

Abstract: Engineered and multimerized human immunodeficiency virus (HIV) envelope glycoproteins are described. The envelope glycoproteins can be multimerized using a heptamerization domain such as a C4b binding protein multimerization domain or a ferritin fusion. The engineered and multimerized envelope glycoproteins can derived from glycoprotein 120 (gp120) and can used as an HIV vaccine.

Abstract: Methods to promote thymic regeneration are described. The methods can inhibit nucleotide-binding oligomerization domain-containing protein 2 (NOD2), Rho GTPases, and/or microRNA 29c (miR29c). These inhibition methods can promote regenerative molecules, such as interleukin (IL)-22, IL-23, and/or bone morphogenetic protein 4 (BMP4). Promoting thymic regeneration can be beneficial in patients due to age, infection, or cancer therapies.

Abstract: The present invention provides a method of carrying out adoptive immunotherapy in a primate subject in need thereof by administering the subject a cytotoxic T lymphocytes (CTL) preparation in a treatment-effective amount. The method comprises administering as the CTL preparation a preparation consisting essentially of an in vitro expanded primate CTL population, the CTL population enriched prior to expansion for central memory T lymphocytes, and depleted prior to expansion of effector memory T lymphocytes. In some embodiments, the method may further comprise concurrently administering Interleukin-15 to the subject in an amount effective to increase the proliferation of the central memory T cells in the subject. Pharmaceutical formulations produced by the method, and methods of using the same, are also described.

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: 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: 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: A platform for ex vivo isolation, production, and formulation of genetically-modified cells is described. The platform utilizes a software-enabled point-of-care and/or portable device making gene therapy more widely available.

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: Systems and methods to modulate the activation state of immune cells in vivo are described. The systems and methods can be used to transform immunosuppressive macrophages that support cancer growth and metastasis into highly activated tumoricidal macrophages.

Abstract: The present disclosure provides compositions, kits, and methods to protect organs by inducing acquired cytoresistance without causing injury to the organ. The compositions, kits, and methods utilize heme proteins, iron and/or vitamin B12 and, optionally, agents that impact heme protein metabolism.

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.