Abstract: Some embodiments of the methods and compositions provided herein relate to the use of hapten labeled cells to stimulate chimeric antigen receptor (CAR) T cells. In some embodiments, CAR T cells can include a CAR that specifically binds to a hapten. Some embodiments relate to the in vivo or in vitro stimulation CAR T cells by hapten labeled cells.

Abstract: Some embodiments provided herein include methods and compositions comprising chimeric antigen receptors (CARs) which specifically bind biotin conjugated to a molecule (conjugated biotin). Some embodiments include therapies for inhibiting, ameliorating, or treating a disorder, such as cancer, in a subject. Some such embodiments include administration of a biotinylated composition, such as conjugated biotin, in combination with the CAR to the subject. In some such embodiments, an immune cell, such as a T cell comprises the CAR.

Abstract: Some embodiments of the methods and compositions provided herein include cells having membrane-tethered, IL13 mutein-directed zetakine receptors, such as those which specifically bind to the IL-13 receptor alpha 2 (IL13Ra2) at a 50-fold higher affinity than wildtype IL-13, and methods of cell-based immunotherapy targeting cancer cells, such as cells of solid tumors, using these compositions. In some embodiments, the receptors include spacer regions, such as particular spacer regions designed to provide certain advantages.

Abstract: Some embodiments provided herein relate to gene delivery systems and methods using a single plasmid that carries a self-inactivating transposase gene and a corresponding transposon. Some embodiments include nucleic acids having certain sequences, vector including such nucleic acids, and compositions including the vectors.

Abstract: Some embodiments of the methods and compositions provided herein include cells having membrane-tethered. IL13 mutein-directed zetakine receptors, such as those which specifically bind to the IL-13 receptor alpha 2 (IL13Ra2) at a 50-fold higher affinity than wild-type IL-13, and methods of cell-based immunotherapy targeting cancer cells, such as cells of solid tumors, using these compositions. In some embodiments, the receptors include spacer regions, such as particular spacer regions designed to provide certain advantages.

Abstract: Embodiments provided herein include methods and compositions comprising anti-dinitrophenol chimeric antigen receptors (CARs). Some embodiments include nucleic acids encoding such CARs, polypeptides encoded by such nucleic acids, cells comprising such nucleic acids or polypeptides, and methods utilizing such cells. Some embodiments also include the use of dinitrophenol (DNP) and derivatives thereof.

Abstract: Methods and compositions for priming a dimerizing agent regulated immunomodulatory complex for signaling by inducing the multimerization of at least a first fusion protein and a second fusion protein to thereby form the dimerizing agent regulated immunomodulatory complex are described. The methods and compositions utilize dimerizing agent dosing schedules designed to: (i) maintain specified blood trough levels of the dimerizing agent, (ii) allow activation of the immunomodulatory complex; (iii) reduce or avoid potential immunosuppressive effects of the dimerizing agent, (iv) reduce or avoid immune cell exhaustion, and/or (v) reduce or avoid side effects associated with activation of the immunomodulatory complex.

Abstract: Aspects of the invention described herein, concern approaches to make genetically modified T-cells comprising a chimeric antigen receptor for human therapy. In some alternatives, the methods utilize a selection and/or isolation of CD4+ and/or CD8+ T-cells from a mixed T-cell population, such as, peripheral blood or apheresis derived mononuclear cells. Once selected/isolated, the CD4+ and/or CD8+ T-cells are then activated, genetically modified, and propagated, preferably, in separate or isolated cultures in the presence of one or more cytokines, which support survival, engraftment and/or proliferation of the cells, as well as, preferably promoting or inducing the retention of cell surface receptors, such as CD62L, CD28, and/or CD27.

Abstract: The present disclosure relates to methods of treating a patient with a cancer by administering to the patient a composition comprising CAR T cells wherein the CAR T cells comprise a CAR and the CAR comprises an E2 anti-fluorescein antibody fragment, and administering to the patient a small molecule linked to a targeting moiety by a linker. The disclosure also relates to compositions for use in such methods.

Abstract: Embodiments of the disclosure include methods of manufacturing compositions comprising host cells. In some alternatives, a method comprises introducing into a host cell an isolated nucleic acid, such as a nucleic acid coding for an isolated polypeptide of an extracellular domain (ECD) of HER2 polypeptide. Some embodiments include culturing the host cells in a medium comprising at least one growth factor. Some embodiments include selecting the host cells for expression of ECD.

Abstract: Recombinant receptors with a binding domain that binds B cell activation factor receptor (BAFF-R) are disclosed. Recombinant receptors include chimeric antigen receptors (CAR) having an anti-BAFF-R binding domain, a transmembrane domain, a CD3?/4-1BB intracellular signaling domain, and a spacer. Methods and systems to treat BAFF-R-expressing cancers, such as mantle cell lymphoma (MCL), multiple myeloma (MM), acute lymphoblastic leukemia (ALL), and diffuse large B-cell lymphoma (DLBCL), are also provided. The recombinant receptors disclosed herein can bind and elicit cytotoxic effects even in low antigen density conditions.

Abstract: A non-immunogenic selection epitope may be generated by removing certain amino acid sequences of the protein. For example, a gene encoding a truncated human epidermal growth factor receptor polypeptide (EGFRt) that lacks the membrane distal EGF-binding domain and the cytoplasmic signaling tail, but retains an extracellular epitope recognized by an anti-EGFR antibody is provided. Cells may be genetically modified to express EGFRt and then purified without the immunoactivity that would accompany the use of full-length EGFR immunoactivity. Through flow cytometric analysis, EGFRt was successfully utilized as an in vivo tracking marker for genetically modified human T cell engraftment in mice. Furthermore, EGFRt was demonstrated to have cellular depletion potential through cetuximab mediated antibody dependent cellular cytotoxicity (ADCC) pathways.

Abstract: The present disclosure relates to methods of treating a patient with a cancer by administering to the patient a composition comprising CAR T cells and administering to the patient a small molecule linked to a targeting moiety by a linker. The disclosure also relates to compositions for use in such methods.

Abstract: Some embodiments of the methods and compositions provided herein relate to chimeric cytokine receptors. In some embodiments, a chimeric cytokine receptor can include an IL-7 domain and/or an IL-21 domain. In some embodiments, the chimeric receptor can include a hybrid IL- 7 and IL-21 cytokine receptor. In some embodiments, the chimeric receptor is capable of combinatorial interleukin signaling when combined with a T cell. In some embodiments, a T cell containing a chimeric cytokine receptor can be readily activated and/or expanded in the absence of an exogenous cytokine.

Abstract: Aspects described herein pertain to engineered chimeric antigen receptors (CARs) and compositions thereof having specificity and affinity for fluorescein containing ligands presented on the surface of tumor cells. Also provided herein are compositions including CARs further comprising a spacer arm and methods of making and using these compositions.

Abstract: A CD19-OR-CD20 chimeric antigen receptor (CAR) protein construct is provided. Also provided are nucleic acids encoding the CD19-OR-CD20 CAR; and methods of use, e.g. in the treatment of B cell malignancies. The CD19-OR-CD20 CAR of the invention is a bispecific CAR that can trigger T-cell activation upon detection of either CD19 or CD20 (or both). It is a single molecule that confers two-input recognition capability upon human T cells engineered to stably express this CAR.

Abstract: Embodiments of the methods and compositions provided herein relate to chimeric antigen receptors (CARs) that specifically bind to B7H3. Some embodiments relate to cell-based immunotherapy targeting tumors, such as tumors comprising B7H3+ cells.

Abstract: The present disclosure relates to methods of treating a patient with a cancer by administering to the patient a composition comprising CAR T cells wherein the CAR T cells comprise a CAR and the CAR comprises an E2 anti-fluorescein antibody fragment, and administering to the patient a small molecule linked to a targeting moiety by a linker. The disclosure also relates to compositions for use in such methods.

Abstract: Aspects of the invention described herein include methods of treating, inhibiting, ameliorating and/or eliminating a virus or cancer cells in a subject utilizing genetically engineered human T-cells having receptors for a molecule presented by the virus or the cancer cells, wherein the genetically engineered T cells are isolated utilizing a two-stage MTX selection that employs increasing concentrations of MTX.

Abstract: Activity-inducible fusion proteins including a transcription factor and a heat-shock protein 90 (hsp90) binding domain are described. The activity of the transcription factor is regulated utilizing a drug molecule that binds the hsp90 binding domain. In the absence of the drug molecule, the transcription factor is in an inactive state but can be activated in the presence of the drug molecule. The activity-inducible transcription factors can be used to alter the activation state of immune cells, and optionally can be co-expressed with a chimeric antigen receptor (CAR).