231 results about "Lymphoblastic Leukemia" patented technology

The present invention is directed to universal T cells and their use in treating diseases and other physiological conditions. More specifically, the present invention is directed to universal T cells and their use in treating treating B-lineage acute lymphoblastic leukemia (B-ALL) in particular and malignancy in general. The universal T cells contain (i) nucleic acid encoding a chimeric antigen receptor (CAR) to redirect their antigen specificity and effector function and (ii) nucleic acids encoding shRNA and/or siRNA molecules to down-regulate cell-surface expression of T cell classical HLA class I and/or II genes to avoid recognition by recipient T cells. The universal T cells may also contain a nucleic acid encoding a non-classical HLA gene, such as an HLA E gene to enforce expression of HLA E genes and/or an HLA G gene to enforce expression of HLA G genes, to avoid recognition by recipient NK cells. The universal T cells may further contain a nucleic acid encoding a selection-suicide gene.

The present invention provides antigen binding proteins that specifically bind to Wilms' tumor protein (WT1), including humanized, chimeric and fully human antibodies against WT1, antibody fragments, chimeric antigen receptors (CARs), fusion proteins, and conjugates thereof. The antigen binding proteins and antibodies bind to HLA-A0201-restricted WT1 peptide. Such antibodies, fragments, fusion proteins and conjugates thereof are useful for the treatment of WT1 associated cancers, including for example, breast cancer, ovarian cancer, prostate cancer, chronic myelocytic leukemia, multiple myeloma, acute lymphoblastic leukemia (ALL), acute myeloid/myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). In more particular embodiments, the anti-WT1/A antibodies may comprise one or more framework region amino acid substitutions designed to improve protein stability, antibody binding and/or expression levels.

The present invention provides methods for treating, reducing the severity, or inhibiting the growth of cancer (e.g., a B-cell cancer such as Hodgkin's lymphoma or acute lymphoblastic leukemia). The methods of the present invention comprise administering to a subject in need thereof a therapeutically effective amount of an antibody or antigen-binding fragment thereof that specifically binds to programmed death 1 (PD-1) receptor in combination with a therapeutically effective amount of a bispecific antibody that specifically binds to CD20 and CD3.

CD20 is a transmembrane protein of the tetra-spanin family expressed on the surface of B-cells and has been found on B-cells from peripheral blood as well as lymphoid tissues. CD20 expression persists from the early pre-B cell stage until the plasma cell differentiation stage. Conversely, it is not found on hematopoietic stem cells, pro-B cells, differentiated plasma cells or non-lymphoid tissues. In addition to expression in normal B-cells, CD20 is expressed in B-cell derived malignancies such as non-Hodgkin's lymphoma (NHL) and B-cell chronic lymphocytic leukemia (CLL). CD20 expressing cells are known to play a role in other diseases and disorders, including inflammation. The present invention includes anti-CD20 antibodies, forms and fragments, having superior physical and functional properties; immunoconjugates, compositions, diagnostic reagents, methods for inhibiting growth, therapeutic methods, improved antibodies and cell lines; and polynucleotides, vectors and genetic constructs encoding same.

Methods for assessing a pathological condition in a subject include measuring one or more markers where a difference is indicative of acute lymphoblastic leukemia (ALL) or a predisposition to ALL, uses and compositions are disclosed.

The present invention provides a method for treating a subject having chronic lymphocytic leukemia (CLL) comprising administering to the subject one or more agents that target cell surface membrane antigens expressed preferentially on cells of the proliferative compartment of a CLL clone of the subject to treat chronic lymphocytic leukemia in the subject. The present invention also provides a method for treating a subject having chronic lymphocytic leukemia comprising administering to the subject one or more agents that target cell surface membrane antigens expressed preferentially on cells of the “resting re-entry compartment” to treat chronic lymphocytic leukemia in the subject.

Differential Methylation Hybridization (DMH) was used to identify novel methylation markers and methylation profiles for hematopoieetic malignancies, leukemia, lymphomas, etc. (e.g., non-Hodgkin's lymphomas (NHL), small B-cell lymphomas (SBCL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL), chronic lymphocytic leukemia (CLL), multiple myeloma (MM), acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), etc.). Particular aspects provide novel biomarkers for NHL and subtypes thereof (e.g., MCL, B-CLL/SLL, FL, DLBCL, etc.), AML, ALL and MM, and further provide non-invasive tests (e.g. blood tests) for lymphomas and leukemias. Additional aspects provide markers for diagnosis, prognosis, monitoring responses to therapies, relapse, etc., and further provide targets and methods for therapeutic demethylating treatments. Further aspects provide cancer staging markers, and expression assays and approaches comprising idealized methylation and/or patterns” (IMP and/or IEP) and fusion of gene rankings.

The invention provides compositions and methods for determining a prognosis of a B cell chronic lymphocytic leukemia (CLL) in a subject based on the level of expression of at least one marker gene. Marker genes provided by the invention are SEPTlO, KIAA0799, Hs.23133, and ADAM29. The marker genes can be used to differentially diagnose CLL in a subject based on relative gene expression levels in the subject compared to reference gene expression levels established from a clinically characterized population of patients. The invention also provides diagnostic reagents and compositions and kits based on the marker genes.

This invention provides methods and kits for diagnosing, ascertaining the clinical course of minimal residual disease associated with acute lymphoblastic leukemia (ALL). Specifically the invention provides methods and kits useful in the diagnosis and determination of clinical parameters associated with diseases associated with ALL based on patterns of surface marker expression unique to ALL.

Methods for treating patients having an early B cell derived acute lymphoblastic leukemia with rapamycin or a derivative thereof are provided. Also provided are methods for treating patients having an early B cell derived acute lymphoblastic leukemia with rapamycin or a derivative thereof in combination with an IL-7 inhibitor. Finally methods for preventing GVHD in ALL patients following a bone marrow transplant are disclosed.

The invention discloses a self-assembled nucleic-acid aptamer/protein composite nano probe, a preparation method, a kit and application thereof. According to the invention, three DNA probes, one of which is a DNA probe containing a nucleic-acid aptamer sequence and another is marked with horseradish peroxidase, are hybridized to prepare a self-assembled nucleic-acid aptamer/protein composite nanoprobe; and magnetic nano-particles functionalized by a nucleic-acid aptamer are used as magnetic separation solid-phase carriers for specific capture of human acute lymphoblastic leukemia T lymphocytes (CCRF-CEM) in blood, to improve the capture efficiency of target substances. When the magnetic nano-particles are used in combination with the self-assembled nucleic-acid aptamer/protein composite nano probe, the detection of CCRF-CEM has a wide linear range, a low detection limit, and high precision and accuracy, and high-sensitivity, high-specificity and rapid detection of CCRF-CEM in peripheral blood samples can be realized, which has great significance for auxiliary diagnosis, curative effect evaluation and prognosis judgment of leukemia.

The invention discloses a kit for quantitatively detecting a BCR/ABL mRNA level. The kit comprises a standard product which is used for manufacturing a standard curve, an inner reference gene real-time quantitative PCR system and at least one of the following three real-time quantitative PCR systems: an M-type BCR/ABL real-time quantitative PCR system, m-type BCR/ABL real-time quantitative PCR system and a mu-type BCR/ABL real-time quantitative PCR system. The kit can accurately, quickly and quantitatively detect various BCR/ABL mRNA levels, is used for diagnosing chronic myelogenous leukemia and acute lymphoblastic leukemia expressed by BCR/ABL and monitoring minimal residual diseases in a treatment process, and provides an important molecular basis for accurate diagnosis of clinical diseases, determination of a treatment proposal, curative effect evaluation and prognosis.

The invention discloses an anti-CD19 engineering antibody and its application which is used in target direction combining lymphocytic leukemia cell. It lays a foundation for the next trituration genetic engineering medicine of the target direction therapy leukemia. It relates to anti-CD19 monoclonal antibody HI19a heavy and light chain variable region gene, and application of the gene code polypeptide, the gene carrier, and using the gene and polypeptide to make leukemia therapy medicine. The heavy and light chain variable region gene is come from the anti-CD19 monoclonal antibody HI19a. The invention successfully adopts gene engineering technique to make anti-CD19 gene engineering antibody, and lays a foundation for the target direction therapy of the leukemia.

The chemokine receptor CXCR4 is a co-receptor for T-tropic strains of HIV-1. A number of small molecule antagonists of CXCR4 are in development, but all are likely to lead to adverse effects due to the physiological function of CXCR4. To prevent these complications, allosteric agonists may be therapeutically useful as adjuvant therapy in combination with small molecule antagonists. A synthetic cDNA library coding for 160,000 different SDF-based peptides was screened for CXCR4 agonist activity in a yeast strain expressing functional receptor. Peptides that activated CXCR4 in an autocrine manner induced colony formation. Two peptides, designated RSVM and ASLW, were identified as novel agonists that are insensitive to the CXCR4 antagonist AMD3100. In chemotaxis assays using the acute lymphoblastic leukemia cell line CCRF-CEM, RSVM behaves as a partial agonist and ASLW as a superagonist. The superagonist activity of ASLW may be related to its inability to induce receptor internalization. In CCRF-CEM cells, the two peptides are also not inhibited by another CXCR4 antagonist, T140, or the neutralizing monoclonal antibodies 12G5 and 44717.111. These results suggest that alternative agonist binding sites are present on CXCR4 that could be screened to develop molecules for therapeutic use.

The invention discloses a B7.1-CD19scFv merge gene engineering protein and usage to treat B lymphocyte leukosis, lymph tumor, which comprises the following parts: human B7.1 external cell area, antihuman CD19 monoclonal antibody heavy chain and light chain variable area gene.

Provided are isolated and purified preparations of a combination of a light chain antibody gene and a heavy chain antibody gene, where the light chain and heavy chain antibody genes are the same among more than one patient with B cell chronic lymphocytic leukemia (B-CLL). Vectors comprising those genes and cells comprising those vectors are also provided, as are isolated and purified antibodies encoded by the antibody genes. Anti-idiotype antibodies, peptides, and aptamers that bind to the antigen-binding region of an antibody encoded by the antibody genes are additionally provided, as are multimeric molecules comprising multiple binding sites that bind to the antigen-binding region of an antibody encoded by the antibody genes. Methods of determining whether a patient with B cell chronic lymphocytic leukemia (B-CLL) has a form of B-CLL that is susceptible to treatment directed to eliminating idiotype specific B cell receptor-bearing B-CLL cells are also provided, as are methods of following the progression of treatment of B-CLL in the patient. Additionally, methods of treating a patient having B-CLL are provided, as are methods of identifying a therapeutic agent for B-CLL.

The present invention encompasses methods and compositions useful in the diagnosis and treatment of drug resistant leukemia. The invention provides a number of genes that are differentially expressed between drug resistant and drug sensitive acute lymphoblastic leukemia (ALL). These genes act as biomarkers for drug resistant leukemia, and further serve as molecular targets for drugs useful in treating drug resistant leukemia. Accordingly, the invention provides methods of diagnosing drug resistant leukemia and methods of selecting a therapy for subjects affected by drug-resistant leukemia. The invention also provides methods for screening for compounds for treating drug-resistant leukemia, and improved methods for treating drug-resistant leukemia. Compositions of the invention include arrays, computer readable media, and kits for use in the methods of the invention.

The present invention relates to combination therapies with anti-CD38 antibodies.

Patients who develop increased numbers of γδ+ cytotoxic T lymphocytes 2–6 months after allogeneic bone marrow transplantation are less likely to relapse than those who do not. The γδ+ T cells isolated from blood of patients with increased γδ+ T cells are CD3+CD4−CD8−CD57+, cytolytic to K562 cells, and express the Vδ1 T cell receptor phenotype. Similar γδ+ T cells can be generated in vitro by culture of donor mononuclear cells which are enriched for γδ+ T cells by immunomagnetic depletion of depleted of CD4+ and CD8+ cells. This γδ-enriched cell preparation was cultured on a combination of immobilized pan-δ monoclonal antibody and irradiated recipient B cell leukemia. After four weeks, the cultures were almost exclusively Vδ1+CD3+CD4−CD8− cells that co-expressed activation-associated antigens CD69, CD25, and HLA-DR. Furthermore, they were cytolytic against the primary leukemia obtained from the recipient and lymphoblastic leukemia cell lines, yet had minimal cytotoxicity against normal donor-derived mononuclear cells or myeloid leulemia cell lines. These observations suggest that donor-derived cytotoxic γδ+ T cells can be generated in vitro, and may provide therapeutic potential for prevention of disease relapse.

The present invention relates to methods of using the expression of ILTL3 ligand or ILT3 on certain types of cancer cells as a diagnostic tool. Methods are provided for treating ILT3-ligand expressing cancers, such as T-cell acute lymphoblastic leukemia (T-cell acute lymphoblastic leukemia), for example by administering ILT3, the extracellular domain of ILT3 or ILT3Fc conjugated to a cytotoxic agent to kill the targeted cancer cell. Other methods are provided for treating cancers that express ILT3 on their surface, such as monocytic forms of AML, for example by administering anti-ILT3 antibodies conjugated to a cytotoxic agent.

The present invention relates to a method for the treatment, amelioration or elimination of acute lymphoblastic leukemia (ALL), the method comprising the administration of a pharmaceutical composition comprising a CD19xCD3 bispecific single chain antibody construct to an adult patient in the need thereof.