Abstract: Described herein are single vectors that, when expressed in cytolytic immune cells, results in both the expression of (1) a CAR targeting tumor-associated antigens and (2) secretion of a bispecific antibody that on one end recognizes NKG2D expressed on both innate and antigen specific cytolytic immune cells and on the other end targets tumor associated antigens. Unexpectedly, these modifications to the T cells result in enhanced survival and proliferation in vivo. Thus, therapeutic and diagnostic uses are disclosed.

Abstract: Disclosed herein are methods, reagents, and pharmaceutical compositions for modulating immune effector cell activation that does not require an antigen-specific antibody. The IgG Fc region is shown herein to contain both a domain that binds an Fc?R on immune effector cells and a non-overlapping region or domain that can bind Fc binding proteins on target cells, and that it is capable of bridging immune effector cells and target cells expressing Fc binding proteins without use of the antigen-binding region (Fab) of the antibody. Therefore, also disclosed are methods of enhancing or inhibiting passive ADCC in subjects.

Abstract: Provided herein are boronic acid esters of boronic acid therapeutic agents, such as bortezomib. The boronic acid esters can be used to prepare liposomal formulations of boronic acid therapeutic agents with improved properties, such as enhanced stability. This disclosure, in one aspect, relates to compositions and methods of making and using the compositions.

Abstract: A polypeptide is disclosed that binds tumor-associated antigens (TAA) on the surface of cancer cells and a NKG2D receptor. The NKG2D receptor is expressed on the surfaces of killer cells such as natural killer cells, T cells, natural killer T cells, and gamma delta T cells. In some cases, the TAA is CS-1 or EGFRvIII. Also disclosed are polynucleotides encoding the disclosed polypeptides, vectors comprising the disclosed polynucleotides, and host cells comprising the disclosed vectors. Also disclosed are bivalent antibodies comprising the disclosed polypeptides. Also disclosed are pharmaceutical compositions comprising the disclosed antibodies. Also disclosed are methods of treating cancer in a subject using the disclosed bi-specific antibodies.

Abstract: Disclosed are methods of mobilizing hematopoietic cells in a subject by administering to the subject a combination of Flt3 ligand (FLT3L) and a cell adhesion inhibitor. Also disclosed are methods of mobilizing hematopoietic cells in a cell culture population by contacting the cell culture population with Flt3 ligand. Mobilized hematopoietic cells can subsequently be harvested and used for hematopoietic cell transplantation. Further disclosed are compositions comprising a FLT3L, compositions comprising FLT3L and a cell adhesion inhibitor, and composition comprising FLT3L and Plerixafor.

Abstract: CAR cells targeting FLT3 relevant antigens are described as a new method of cancer treatment. It is proposed that FLT3 CAR cells are safe and effective in patients and can be used to treat human tumors and cancer.

Abstract: Glioblastoma (GB) remains the most aggressive primary brain malignancy; brain metastasis, such as breast cancer brain metastases (BCBMs), are also aggressive and are associated with poor prognosis. Adoptive transfer of chimeric antigen receptor (CAR)-modified immune cells has emerged as a promising anti-cancer approach, yet the potential utility of CAR-engineered cells to treat brain cancers has not been explored. The present disclosure presents compostions and methods for using CAR expressing cells in the treatment of various cancers, including brain cancers such as GB and BCBMs.

Abstract: Methods and compositions involving miR-122, miR-15b, miR-21, and miR-155, which are useful for the treatment of various diseases, such as cancers, are described. Further described are methods and compositions useful for increasing, activating, or regulating NK cells and surface antigens.

Abstract: Provided herein are boronic acid esters of boronic acid therapeutic agents, such as bortezomib. The boronic acid esters can be used to prepare liposomal formulations of boronic acid therapeutic agents with improved properties, such as enhanced stability. This disclosure, in one aspect, relates to compositions and methods of making and using the compositions.

Abstract: Methods and compositions involving miR-122, miR-15b, miR-21, and miR-155, which are useful for the treatment of various diseases, such as cancers, are described. Further described are methods and compositions useful for increasing, activating, or regulating NK cells and surface antigens.

Abstract: Disclosed are methods of mobilizing hematopoietic cells in a subject by administering to the subject a combination of Flt3 ligand (FLT3L) and a cell adhesion inhibitor. Also disclosed are methods of mobilizing hematopoietic cells in a cell culture population by contacting the cell culture population with Flt3 ligand. Mobilized hematopoietic cells can subsequently be harvested and used for hematopoietic cell transplantation. Further disclosed are compositions comprising a FLT3L, compositions comprising FLT3L and a cell adhesion inhibitor, and composition comprising FLT3L and Plerixafor.

Abstract: Methods for stably transfecting mammalian natural killer cells comprising: transfecting a packaging cell line with a retroviral expression vector; culturing the transfected packaging cell line in a cell culture medium; and culturing the mammalian natural killer cells with the cell culture medium. Natural killer cells transfected according to the disclosed methods are also provided.

Abstract: The present invention provides isolated cells that are selectively enriched for hematopoietic progenitor cells that are precursors for natural killer (NK) cells. These cells are both CD34 and CD45RA positive and express C-integrin ?7, and are referred to as CD34dimCD45RA(+)C-integrin ?7bright. The invention provides methods for isolating these cells, for inducing formation of CD56bright NK cells, and for treating diseases associated with immunodeficiency and cancer.

Abstract: The disclosure relates to methods to prevent, treat, or slow the progression viral-associated lymphoproliferative disorders, EBV-associated lymphoproliferative disorders, and post-transplant lymphoproliferative disorders. In the methods, a TGF-? antagonist, e.g., an anti-TGF-? antibody is administered to a subject. Methods for treating viral-associated lymphoproliferative disorders and for enhancing T-cell responsiveness to a viral-associated lymphoproliferative disorder by administering a TGF-? antagonist are also described.

Abstract: Methods for stably transfecting mammalian natural killer cells comprising: transfecting a packaging cell line with a retroviral expression vector; culturing the transfected packaging cell line in a cell culture medium; and culturing the mammalian natural killer cells with the cell culture medium. Natural killer cells transfected according to the disclosed methods are also provided.

Abstract: A CD34(+) cell line, which can be found in human lymph nodes, called CD34dimCD45RA(+)integrin?7bright. Methods of isolating the novel cell type from tissue and methods of its use are also provided.

Abstract: Methods for treating a subject with a cancer that is characterized by overexpression of HER2 receptor protein using a combination of interleukin-2 (IL-2) or variant thereof and at least one anti-HER2 antibody or fragment thereof are provided. These anti-tumor agents are administered as two separate pharmaceutical compositions, one containing IL-2 (or variant thereof), the other containing at least one anti-HER2 antibody (or fragment thereof), according to a dosing regimen. Administering of these two agents together potentiates the effectiveness of the anti-HER2 antibody alone, resulting in a positive therapeutic response that is improved with respect to that observed with this anti-tumor agent.

Abstract: Methods for treating a subject with a cancer that is characterized by overexpression of HER2 receptor protein using a combination of interleukin-2 (IL-2) or variant thereof and at least one anti-HER2 antibody or fragment thereof are provided. These anti-tumor agents are administered as two separate pharmaceutical compositions, one containing IL-2 (or variant thereof), the other containing at least one anti-HER2 antibody (or fragment thereof), according to a dosing regimen. Administering of these two agents together potentiates the effectiveness of the anti-HER2 antibody alone, resulting in a positive therapeutic response that is improved with respect to that observed with this anti-tumor agent.

Abstract: Methods of vaccination to prevent virus-associated diseases, which methods generally result in an increase of virus-specific memory T cells that provide or restore host immunity and result in control of the viral-associated disease process. Polypeptides and DNA sequences for achieving these results are also described. In some embodiments, the virus is Epstein-Barr virus.

Abstract: Cell preparations comprising a plurality of apoptotic EBV-transformed B lymphocytes, and methods of producing cell preparations comprising a plurality of apoptotic EBV-transformed B lymphocytes are provided. The methods comprise transforming B lymphocytes with EBV, incubating the transformed B lymphocytes with a flavin photosensitizer, such as riboflavin or a lumichrome-resistant photosenstizer, adding a non-toxic anti-oxidant, and exposing the lymphocytes to photoradiation of an appropriate wavelength to activate the photosensitizer. Also provided are methods of using the apoptotic EBV-transformed B lymphocyte cell preparations to elicit production of EBV-specific T cells in human patients. Finally, methods of treating organ transplant patients comprising administering an effective amount of the apoptotic EBV-transformed B-lymphocytes cell preparation to the patients prior to transplantation are provided.