Abstract: Regulatory T cells (Treg) limit autoimmunity but can also attenuate the magnitude of anti-pathogen and anti-tumor immunity. Understanding the mechanism of Treg function and therapeutic manipulation of Treg in vivo requires identification of Treg selective receptors. A comparative analysis of gene expression arrays from antigen specific CD4+ T cells differentiating to either an effector/memory or a regulatory phenotype revealed Treg selective expression of LAG-3 (CD223), a CD4-related molecule that binds MHC class II. LAG-3 expression on CD4+ T cells correlates with the cells' in vitro suppressor activity, and ectopic expression of LAG-3 on CD4 T cells confers suppressor activity on the T cells. Antibodies to LAG-3 inhibit suppression both in vitro and in vivo. LAG-3 marks regulatory T cell populations and contributes to their suppressor activity.

Abstract: Regulatory T cells (Treg) limit autoimmunity but can also attenuate the magnitude of anti-pathogen and anti-tumor immunity. Understanding the mechanism of Treg function and therapeutic manipulation of Treg in vivo requires identification of Treg selective receptors. A comparative analysis of gene expression arrays from antigen specific CD4+ T cells differentiating to either an effector/memory or a regulatory phenotype revealed Treg selective expression of LAG-3 (CD223), a CD4-related molecule that binds MHC class II. LAG-3 expression on CD4+ T cells correlates with the cells' in vitro suppressor activity, and ectopic expression of LAG-3 on CD4 T cells confers suppressor activity on the T cells. Antibodies to LAG-3 inhibit suppression both in vitro and in vivo. LAG-3 marks regulatory T cell populations and contributes to their suppressor activity.

Abstract: The present invention relates to a chimeric receptor capable of signaling both a primary and a co-stimulatory pathway, thus allowing activation of the co-stimulatory pathway without binding to the natural ligand. The cytoplasmic domain of the receptor contains a portion of the 4-1BB signaling domain. Embodiments of the invention relate to polynucleotides that encode the receptor, vectors and host cells encoding a chimeric receptor, particularly including T cells and natural killer (NK) cells and methods of use.

Abstract: Combinations of anti-cancer vaccines and inhibitory antibodies to CD223 overcome immune suppression in cancer patients. The vaccines may be isolated antigens, groups of antigens, or whole tumor cells. The inhibitory antibodies may be generated in an animal by injection of fragments of CD223. Antibodies may be monoclonal antibodies or single chain antibodies or humanized antibodies.

Abstract: The present invention relates to a chimeric receptor capable of signaling both a primary and a co-stimulatory pathway, thus allowing activation of the co-stimulatory pathway without binding to the natural ligand. The cytoplasmic domain of the receptor contains a portion of the 4-1BB signaling domain. Embodiments of the invention relate to polynucleotides that encode the receptor, vectors and host cells encoding a chimeric receptor, particularly including T cells and natural killer (NK) cells and methods of use.

Abstract: The present invention relates to a chimeric receptor capable of signaling both a primary and a co-stimulatory pathway, thus allowing activation of the co-stimulatory pathway without binding to the natural ligand. The cytoplasmic domain of the receptor contains a portion of the 4-1BB signaling domain. Embodiments of the invention relate to polynucleotides that encode the receptor, vectors and host cells encoding a chimeric receptor, particularly including T cells and natural killer (NK) cells and methods of use.

Abstract: Single nucleotide polymorphisms (SNPs) in the gene encoding gamma glutamyl hydrolase (GGH) associated with reduced GGH activity are disclosed. The primary SNP is a change from a cytosine to a thymine at a position corresponding to nucleotide 511 of Genbank sequence accession no. NM 003878. Methods and kits for detecting these SNPs are provided, along with primers useful in detecting these SNP and for amplifying portions of the GGH gene containing these SNPs.

Abstract: A laboratory rack assembly for supporting columns and receptacle tubes and other paraphernalia during laboratory procedures such as such as filtration, chromatography, plasma preparation, affinity purification, and so on, includes upper and lower support portions that are connected together for relative sliding movement. An upper rack module is connected to the upper support portion and is configured to receive at least one column. A lower rack module is connected to the lower support portion and is configured to receive at least one receptacle tube. At least one of the rack modules is removably connected to at least one of the support portions. An adjustment mechanism is operably associated with the upper and lower support portions for adjusting a position of one support portion with respect to the other support portion to thereby vary the distance between the upper and lower rack modules.

Abstract: Combinations of anti-cancer vaccines and inhibitory antibodies to CD223 overcome immune suppression in cancer patients. The vaccines may be isolated antigens, groups of antigens, or whole tumor cells. The inhibitory antibodies may be generated in an animal by injection of fragments of CD223. Antibodies may be monoclonal antibodies or single chain antibodies or humanized antibodies.

Abstract: Single nucleotide polymorphisms (SNPs) in the gene encoding gamma glutamyl hydrolase (GGH) associated with reduced GGH activity are disclosed. The primary SNP is a change from a cytosine to a thymine at a position corresponding to nucleotide 511 of Genbank sequence accession no. NM 003878. Methods and kits for detecting these SNPs are provided, along with primers useful in detecting these SNP and for amplifying portions of the GGH gene containing these SNPs.

Abstract: The present invention discloses that the binding of Arf with Dm2, important components of the p53 tumor suppressor pathway, results in specific domains of both proteins undergoing a dramatic transition from dynamically disordered conformations to amyloid-like structures comprised of anti-parallel ?-strands. The invention exploits this discovery by providing unique methods for identifying and/or designing compounds that mimic, inhibit and/or enhance the effect of Arf on Dm2. The present invention also provides specific peptides derived from the binding domains of Arf and Dm2 which co-assemble into supramolecular structures comprised of binary anti-parallel ?-strands. The disclosed peptides may represent structural prototypes for a broader class of peptides that is capable of assembly into supramolecular structures.

Abstract: The present invention relates to novel methods for preferentially activating and expanding NK cells. The methods utilize the stimulatory effects of IL-15 and CD137 ligand to preferentially expand and activate NK cells in a mixed cell culture comprising NK cells.

Abstract: The invention relates to human nucleotide sequences which occur as a result of the t(1;22)(p13;q13) chromosomal translocation event which is known to occur almost invariable in young children with acute megakaryoblastic leukemia. The translocation results in the formation of fusion genes which encode fusion proteins. The invention provides the nucleotide sequences of transcripts of the fusion genes and the amino acid sequences of the fusion proteins encoded thereby. Also provided are methods for detecting the t(1, 22) translocation, for identifying agents capable of binding to the fusion protein and for identifying agents useful for treating patients with acute megakaryoblastic leukemia.

Abstract: A presentation application and database development and management controller, collectively, produce an individual or group-specific, customized interface to a shared database. The presentation application can be template or script driven, and interacts with each client to provide a customized display. In an embodiment, the presentation application communicates with a network server to distribute data to clients over a computer network, such as the global Internet. The database development and management controller interacts with the database and manages the customization and distribution of data to the presentation application. A collection of service objects are built to represent the information stored in the database. A plurality of presentation objects are also provided as abstract representations used to organize and customize the display of the information. As such, one or more service objects are mapped to each presentation object.

Abstract: Regulatory T cells (Treg) limit autoimmunity but can also attenuate the magnitude of anti-pathogen and anti-tumor immunity. Understanding the mechanism of Treg function and therapeutic manipulation of Treg in vivo requires identification of Treg selective receptors. A comparative analysis of gene expression arrays from antigen specific CD4+ T cells differentiating to either an effector/memory or a regulatory phenotype revealed Treg selective expression of LAG-3 (CD223), a CD4-related molecule that binds MHC class II. LAG-3 expression on CD4+ T cells correlates with the cells' in vitro suppressor activity, and ectopic expression of LAG-3 on CD4 T cells confers suppressor activity on the T cells. Antibodies to LAG-3 inhibit suppression both in vitro and in vivo. LAG-3 marks regulatory T cell populations and contributes to their suppressor activity.

Abstract: The invention relates to methods for detecting genetic polymorphisms in an organism, particularly to the detection of genetic polymorphisms that are due to multiple distal nucleotide polymorphisms within a gene. Methods are provided for determining the haplotype structure of a gene, or other contiguous DNA segment, having two or more nucleotide polymorphisms that are separated by kilobases of DNA. The methods involve the use of PCR amplification and DNA ligation to bring the nucleotide polymorphisms on a particular allele of the gene into close proximity to facilitate the determination of haplotype structure.

Abstract: Methods and compositions based on the elucidation of the role of Prox1 in lymphatic tissue development in normal and tumor tissue are provided. Included are methods for determining the extent of lymphatic involvement in a tumor, methods for purifying endothelial precursor cells predisposed to develop into lymphatic tissue, and methods for promoting the development of lymphatic tissue. Pharmaceutical compositions and gene therapy vectors useful in the latter methods are provided.

Abstract: The present invention is based on the discovery that proteins produced in insect cell cultures are glycosylated in a unique manner that causes them to be selectively imported by cells that express mannose receptors on their membranes, particularly macrophages. Proteins that are selectively imported into cells containing mannose receptors are provided, as well as pharmaceutical compositions containing such proteins and methods for producing such proteins. Application of the present invention to produce proteins useful for treating lysosomal storage disorders is also disclosed. Engineering of cells to express mannose receptors so that they will selectively import proteins produced in insect cells is also taught, as well as a protein targeting system using such cells and proteins. Finally, an improved elution buffer for the purification of proteins produced in insect cells from a Concanavalin A column is provided.

Abstract: A general method for identifying biological targets for improving currently available therapies is provided. Target genes and their expression products are identified based on their response to therapy as determined through pre- and post-therapy expression profiles. In another aspect, differences in expression profiles between responsive and nonresponsive patients are taken into account to identify potential new targets for the development of novel medications or treatments. The invention also provides methods for comparing therapies to predict which will have the best therapeutic efficacy and/or the least potential deleterious. The methods taught are specifically applied to identify targets for improving treatment of acute lymphoblastic leukemia.

Abstract: Allelic variation in the vex2, pep27 and vncS genes of bacteria responsible for tolerance to antibiotics such as penicillin and vancomycin, is taught. Methods for identifying antibiotic tolerant bacteria and subjects infected with such bacteria, particularly antibiotic tolerant Streptococcus pneumoniae, are provided. Test kits and components useful for performing such methods, particularly including oligonucleotide primers, are also provided.