Abstract: A cell cultivation apparatus for cultivating microorganisms and growing cells at high density is provided. The apparatus includes a membrane comprising multiple surface features on a first side of the membrane for cell placement. The surface features comprising one or more compartments within which a cell can be located. The membrane includes a material that is at least partially permeable to gas. A second side of the membrane defines a gas region. The second side of the membrane is separated from the first side of the membrane by the membrane. The apparatus further includes a media region for receiving media. The compartments are configured to at least partially reduce media flow shear forces on one or more cells in the compartments. The surface features may be ridges, protrusions, fins, wells, and/or posts.

Abstract: Disclosed herein are conditioning regimens and methods for inducing MHC- or HLA-mismatched mixed chimerism by conditioning a recipient with radiation-free, low-doses of cyclophosphamide (CY), pentostatin (PT), and anti-thymocyte globulin (ATG) prior to transplantation of donor bone marrow cells. In certain embodiments, the donor bone marrow cells may be CD4+ T-depleted bone marrow cells. The conditioning regimens and methods may also include administering one or more populations of conditioning donor cells selected from donor CD4+ T-depleted spleen cells, donor CD8+ T cells, and donor G-CSF-mobilized peripheral blood mononuclear cells. The conditioning regimen is clinically acceptable and can be used for treating hereditary hematological diseases and autoimmune diseases, as well as for promoting organ transplantation immune tolerance.

Abstract: Provided herein are BAFF-R antibodies as well as compositions and methods of making and using the same. The antibodies provided herein are, inter alia, useful for the treatment of cancer and autoimmune diseases.

Abstract: Provided herein are solution formulations of CX-011 and related methods for making solution formulations of CX-011. Also provided are methods of treating an inflammatory disorder, such as osteoarthritis, or cancer in a subject in need thereof by administering an effective amount of the solution formulations of CX-011.

Abstract: Disclosed herein, inter alia, are compounds and methods for inhibiting the thioredoxin-thioredoxin-interacting-protein (TXNIP-TRX) complex.

Abstract: Disclosed herein are, inter alia, inhibitors of protein arginine methyltransferase 9 and pharmaceutical compositions thereof, and methods comprising the use of protein arginine methyltransferase 9 inhibitors for the treatment of a protein arginine methyltransferase 9-modulated disease or disorder, such as a hematological cancer.

Abstract: Disclosed are vaccine compositions comprising a VLP comprising two or more EBV envelope glycoproteins and one or more T cell antigens and methods of preventing or treating EBV infections using the vaccine compositions. Also disclosed is an expression system or a single expression vector for co-expressing two or more EBV envelope glycoproteins simultaneously to generate a VLP vaccine. The expression system may include a single vector inserted with two or more nucleic acid sequences that encode two or more EBV envelope glycoproteins linked by one or more linking sequences such that the EBV envelope glycoproteins are co-expressed simultaneously.

Abstract: Disclosed herein, inter alia, are compounds and methods for inhibiting the thioredoxin-thioredoxin-interacting-protein (TXNIP-TRX) complex.

Abstract: Adeno-associated virus (AAV) Clade F vectors or AAV vector variants (relative to AAV9) for precise editing of the genome of a cell and methods and kits thereof are provided. Targeted genome editing using the AAV Clade F vectors or AAV vector variants provided herein occurred at frequencies that were shown to be 1,000 to 100,000 fold more efficient than has previously been reported. Also provided are methods of treating a disease or disorder in a subject by editing the genome of a cell of the subject via transducing the cell with an AAV Clade F vector or AAV vector variant as described herein and further transplanting the transduced cell into the subject to treat the disease or disorder of the subject. Also provided herein are methods of treating a disease or disorder in a subject by in vivo genome editing by directly administering the AAV Clade F vector or AAV vector variant as described herein to the subject.

Abstract: Disclosed herein are compositions and methods for treating cancer, FLT3-AML, and CML.

Abstract: Provided are compositions and methods for altering gene expression in cells. The compositions and methods may utilize a nucleic acid sequence that has a genetically modified trans-activating crRNA (tracrRNA) sequence, where at least one uracil nucleotide of the tracrRNA sequence is replaced with a nucleotide other than uracil, and/or a nucleic acid sequence that has a guide RNA (gRNA) sequence wherein one or more cytosine nucleotides and/or one or more uracil nucleotides of said gRNA sequence are modified nucleotides. Also provided are methods of treating a disorder in a subject in need of the treatment. The method may involve administering to the subject the nucleic acid or a vector thereof in combination with an RNA-guided DNA endonuclease enzyme.

Abstract: Disclosed is a method of preventing or treating acute GVHD (aGVHD) such as gut aGVHD, steroid-resistant aGVHD, and steroid-resistant gut aGVHD in a subject receiving a hematopoietic cell transplantation (HCT) or autoimmune colitis by administering to the subject an effective amount of an anti-IL-22 antibody, an anti-IL-6 antibody, donor-type CX3CR1hi MNPs, donor-type NK cells, a ceacam-1 antagonist, an anti-Gr-1 antibody, or a combination thereof.

Abstract: The present invention relates to compositions comprising TWIST signaling inhibitors and optionally one or more anti-cancer agents, and methods of using the compositions for the treatment of cancer.

Abstract: Provided herein are recombinant CTLA-4 binding proteins, which are, inter alia, useful for the treatment of cancer. The recombinant proteins provided herein are, inter alia, capable of binding CTLA-4 proteins on a tumor cell. In a first aspect, there is provided a recombinant CTLA-4 binding protein including (i) a CTLA-4 binding domain; (ii) a CTLA-4 binding domain masking peptide; and (iii) a cleavable peptide linker connecting the CTLA-4 binding domain masking peptide to the CTLA-4 binding domain. In another aspect, there is provided a dimerizing domain covalently attached to the CTLA-4 binding domain, wherein the binding protein domains are bound together.

Abstract: A family of chimeric antigen receptors (CARs) containing a CD123 specific scFv was developed to target different epitopes on CD123. In some embodiments, such a CD123 chimeric antigen receptor (CD123CAR) gene includes an anti-CD123 scFv region fused in frame to a modified IgG4 hinge region comprising an S228P substitution, an L235E substitution, and optionally an N297Q substitution; a costimulatory signaling domain; and a T cell receptor (TCR) zeta chain signaling domain. When expressed in healthy donor T cells (CD4/CD8), the CD123CARs redirect T cell specificity and mediated potent effector activity against CD123+ cell lines as well as primary AML patient samples. Further, T cells obtained from patients with active AML can be modified to express CD123CAR genes and are able to lyse autologous AML blasts in vitro. Finally, a single dose of 5.0×106 CAR123 T cells results in significantly delayed leukemic progression in mice.

Abstract: Provided herein are, inter alia, nucleic acid compounds useful for targeting CTLA-4-expressing cells and modulating cell activity of the CTLA-4-expressing cells. The compositions provided herein may be part of pharmaceutical compositions and may be used for treatment of cancer, inflammatory diseases, infectious diseases or metabolic diseases.

Abstract: Provided herein are adeno-associated virus (AAV) compositions that can restore F8 gene function in a cell without co-transducing or co-administering an exogenous nuclease or a nucleotide sequence that encodes an exogenous nuclease. Also provided are methods of using the AAV compositions to correct an F8 gene mutation and/or treat a disease or disorder associated with an F8 gene mutation. Packaging systems for making the adeno-associated virus compositions are also provided.

Abstract: Brachytherapy templates and template holders can be adjustable relative to a patient's anatomy. One template includes a disposable portion with an aperture layer that includes first apertures and a patient contact layer that includes an adhesive on a surface thereof. The patient contact layer is formed from a flexible material. The template also includes a reusable portion that includes aperture plates. A locking mechanism can lock catheters firmly in place. One template holder includes a template compartment retainer constructed to hold a brachytherapy template, and a perineum attachment component is connected to the template compartment retainer by a connecting portion. The perineum attachment component includes a perineum attachment portion formed from a flexible material.

Abstract: Disclosed herein are methods and compositions for inactivation of the human glucocorticoid receptor (GR) gene by targeted cleavage of genomic DNA encoding the GR. Such methods and compositions are useful, for example, in therapeutic applications which require retention of immune function during glucocorticoid treatment.

Abstract: Disclosed is a method of preventing or treating GVHD while preserving GVL activity in a subject receiving a hematopoietic cell transplantation (HCT) by administering to the subject an effective amount of an anti-IL-2 antibody such as an anti-IL-2-JES6 antibody.