19 results about "Macroglobulin" patented technology

Discussed herein are pharmaceutical compositions containing Ibrutinib and processes for preparing them. The compositions may be utilized in the treatment of a variety of conditions including, without limitation, B-cell proliferative disorders such as non-Hodgkin lymphoma (diffuse large B cell lymphoma, follicular lymphoma, mantle cell lymphoma or burkitt lymphoma), Waldenstrom macroglobulinemia, plasma cell myeloma, chronic lymphocytic leukemia, lymphoma, or leukemia. These compositions are designed for oral ingestion. The compositions are contained within a capsule such as a standard or sprinkle or in a liquid formulation such as a suspension. In one embodiment, the pharmaceutical composition contains Ibrutinib, a salt, prodrug, or metabolite thereof, microcrystalline cellulose, croscarmellose sodium, sodium lauryl sulfate, and magnesium stearate. In another embodiment, the pharmaceutical composition contains Ibrutinib, a salt, prodrug, or metabolite thereof, microcrystalline cellulose, carboxymethylcellulose sodium, hydroxypropylmethylcellulose, citric acid monohydrate, disodium hydrogen phosphate, sucralose, sodium methyl parahydroxybenzoate, sodium ethyl parahydroxybenzoate, concentrated hydrochloric acid, sodium hydroxide, and water.

Introduction: Rituximab (R) is an integral component of therapy for B-cell lymphoid malignancies; bortezomib (Btz) has shown provocative single agent activity in Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL) and Waldenstrom's Macroglobulinaemia (WM), providing the rationale for investigating the combination.Patients+Methods: Forty-five adult patients (pts.) (30 men, 15 women) with histologically confirmed recurrent CD20+ve FL, MCL or WM, median age 60 years (range 45-79), FL: 17, MCL: 18, WM: 10, stage III / IV 40 (93%), bone marrow (BM) infiltration 32 (73%), elevated LDH 22 (49%), performance status ≥1 22 (49%), were enrolled in a randomised trial comparing 2 schedules of Brz+R: Arm A (twice weekly) Btz: 1.3 mg / m2 (on days 1, 4, 8, 11 of a 21-day cycle) and R: 375 mg / m2 (on day 1) for 8 cycles, or Arm B (weekly) Btz: 1.6 mg / m2 (on days 1, 8, 15, 22 of a 35-day cycle) and R: 375 mg / m2 (on days 1, 8, 15, 22 of cycles 1 and 4) for 6 cycles (23 arm A, 22 arm B). The median number of previous treatments was 2 (range 1-7). Seventeen pts. had received a R-containing regimen, with response lasting >6 months, and 8 high-dose treatment. Response was evaluated using the IWR criteria (Cheson et al, JCO 17:1244, 1999) and the updated response criteria from the 3rd International Workshop on WM (Treon et al, Blood 107:3442, 2006)Results: Ability to deliver the therapy, toxicity and efficacy were equivalent in both arms. The median number of cycles given in arm A was 4 and 5 in arm B. Haematological toxicity (grade≥3: anaemia 0%, neutropenia 25%, thrombocytopenia 22%) was significantly influenced by the high percentage of pts. with BM infiltration and concomitant cytopenia on entry to the trial. The most common non-haematological adverse events were fatigue (76%), nausea (56%), diarrhoea (56%), lethargy (46%). Neurotoxicity occurred in 19 pts. (46%) (10 pts. grade 1, 7 pts. grade 2, 2 pts. grade 3). Btz dose was reduced in 7 pts.; 5 doses were omitted because of neuro or haematological toxicity. In 16 pts., treatment was delayed by 1-14 days and in 24 pts. treatment was stopped prematurely. The reasons for stopping treatment were: treatment-related toxicity 11 pts., progressive disease 9 pts., patient's preference 3 pts., myocardial infarction 1 pt. One pt. was excluded having been found ineligible post randomisation. Thirty-nine pts. (21 arm A, 18 arm B) are evaluable for response so far, one having only received 1 cycle of therapy, which had to be discontinued because of excessive toxicity. 15 / 32 were in remission (CR, CRu, PR) at the completion of therapy, 7 / 7 at “mid-therapy” assessment, and 5 have yet to be evaluated. Thus the overall response rate (RR) presently is 22 / 39 (56%) (CR, CRu, PR), FL 44%, MCL 46%, WM 90%.Conclusions:The combination was active in pts. with recurrent NHL especially WM (RR 90%), despite multiple previous treatments, The weekly schedule is preferable being more convenient, as efficacious and no more toxic.Further investigation is warranted, despite not insignificant therapy compromising toxicity.

The disclosure features, inter alia, immunogenic XBP1-, CD138-, and CS1-derived peptides (and pharmaceutical compositions thereof). The peptides can be used in a variety of methods such as methods for inducing an immune response, methods for producing an antibody, and methods for treating a cancer (e.g., breast cancer, colon cancer, pancreatic cancer, a blood cancer, e.g., leukemia or a plasma cell disorder such as multiple myeloma or Waldenstrom's macroglobulinemia). The peptides (and pharmaceutical compositions comprising the peptides) can be used, e.g., in a method of treating a precancerous condition such as smoldering multiple myeloma. The peptides can also be included in MHC molecule multimer compositions and used in, e.g., methods for detecting a T cell in a population of cells.

The invention relates to a preparation method and application of alpha2-macroglobulin. The invention finds that the alpha2-macroglobulin can be used for promoting the intercellular effect of cells, and further can be used for preparing medicines for treating osteoarthritis, atherosclerosis, inflammatory aging, tumors, chronic obstructive pulmonary disease, systemic lupus erythematosus and other diseases caused by intercellular function deficiency.

The invention discloses a fusion protein of neutrophil elastase as well as a preparation method and application of the fusion protein. The fusion protein comprises an optimized human neutrophil elastase (ELANE) fragment and an optimized human alpha2-macroglobulin (A2M) fragment; the amino acid sequence of the fusion protein is as shown in SEQ ID NO.8. The use of ELANE is limited due to intolerance to serine protease inhibitors (such as alpha-1-antitrypsin, A1AT). The optimized ELANE fragment and the optimized A2M fragment are connected to form the fusion protein, the fusion protein has high enzymatic activity, the tolerance to A1AT is greatly improved, and 83.3% of enzyme activity can still be maintained after the fusion protein acts for 2 hours through high-concentration A1AT (19200 nM). The fusion protein can efficiently eliminate mouse tumors and is safe to mice. The fusion protein is simple in preparation process and easy to industrially amplify, and a new strategy is provided for tumor treatment.

Discussed herein are pharmaceutical compositions containing Ibrutinib and processes for preparing them. The compositions may be utilized in the treatment of a variety of conditions including, without limitation, B-cell proliferative disorders such as non-Hodgkin lymphoma (diffuse large B cell lymphoma, follicular lymphoma, mantle cell lymphoma or burkitt lymphoma), Waldenstrom macroglobulinemia, plasma cell myeloma, chronic lymphocytic leukemia, lymphoma, or leukemia. These compositions are designed for oral ingestion. The compositions are contained within a capsule such as a standard or sprinkle or in a liquid formulation such as a suspension. In one embodiment, the pharmaceutical composition contains Ibrutinib, a salt, prodrug, or metabolite thereof, microcrystalline cellulose, croscarmellose sodium, sodium lauryl sulfate, and magnesium stearate. In another embodiment, the pharmaceutical composition contains Ibrutinib, a salt, prodrug, or metabolite thereof, microcrystalline cellulose, carboxymethylcellulose sodium, hydroxypropylmethylcellulose, citric acid monohydrate, disodium hydrogen phosphate, sucralose, sodium methyl parahydroxybenzoate, sodium ethyl parahydroxybenzoate, concentrated hydrochloric acid, sodium hydroxide, and water.

The invention discloses a primer blocker composition for detecting a macroglobulinemia Fahrenheit CXCR4 gene, the primer blocker composition comprises a primer group and a blocker, and the primer group comprises a forward primer group and a reverse primer group; the nucleotide sequence of the blocking agent is as shown in SEQ ID NO. 1; the nucleotide sequence of the reverse primer group is as shown in SEQ ID NO. 2; the nucleotide sequence of the forward primer group is as shown in SEQ ID NO. 3. The invention also discloses a kit containing the composition and a detection method. By accurately detecting the CXCR4 gene, the CXCR4 gene can be combined with other markers, and pathological diagnosis and molecular typing of WM are accurate; a plurality of CXCR4 high-frequency mutation sites of WM can be covered by a single reaction, and compared with a digital PCR method only capable of detecting a single site, the cost is reduced by more than 80%, and the method is suitable for being popularized in hospitals.

The application discloses a sugar chain marker combination for diagnosing Waldenstrom's macroglobulinemia and application thereof, and the marker combination comprises the following N-sugar chains: cFA2_2, cFA2B, cFA2(6)G1, cFA2(3)G1, A2G2, cFA2B(3)G1, cFA2G2, cFA2BG2, A3G3_2 and aFA3G3_2. By analyzing the change of N-sugar chains on glycoprotein in blood, the application finds that specific N-sugar chain marker combination has significant correlation with WM. The marker combination has high sensitivity and high specificity in WM diagnosis, can be rapidly detected through fluorescence labeling technology, has a non-invasive advantage, can be used for early discovery and accurate diagnosis, and is helpful to improve the cure rate and survival rate of patients. In addition, the discovery of the bisecting biantennary N-sugar chain combination provides a new potential treatment target for WM, and has important clinical application value.

Provided are pharmaceutical compositions comprising alpha-2-macroglobulin (A2M) and a serine protease protein, such as porcine pancreatic elastase (PPE), which are bound together in a protein complex that retains the CD95 protease cleavage and cancer cell killing activity of the serine protease, but spatially hinders binding of the serine protease to fibrinogen and a serine protease inhibitor; and related use and preparation methods for treating diseases such as cancer.

Disclosed herein are methods for determining whether a subject is suffering from Waldenström macroglobulinemia (WM) or a precursor condition thereof, or multiple myeloma (MM) or a precursor condition thereof. These methods comprise determining, in a sample obtained from the subject, data indicative of the proportions of two or more immune cell populations. Methods of monitoring a subject with WM, or a precursor condition thereof, are also disclosed. These methods comprise determining in tumor cells obtained from a sample obtained from the subject and a reference sample expression of two or more gene expression signatures which indicate whether the subject is at risk of disease progression.

The features of the present disclosure are immunogenic XBP1-derived peptides, CD138-derived peptides, and CS1-derived peptides (and their pharmaceutical compositions), etc. The peptides can be used in a variety of methods, such as methods for inducing an immune response, methods for generating antibodies, and methods for treating cancer (e.g., breast cancer, colon cancer, pancreatic cancer, blood cancers, e.g., leukemia, or plasma cell disorders such as multiple myeloma or Waldenstrom macroglobulinemia). The peptides (and pharmaceutical compositions comprising the peptides) can be used, for example, in methods for treating pre-cancerous conditions such as smoldering multiple myeloma. The peptides can also be incorporated into MHC molecule multimer compositions and used, for example, in methods for detecting T cells in a cell population.

The present invention relates to a method for diagnosing the risk of non-alcoholic steatohepatitis (NAS) in a human patient with a metabolic disorder, comprising: (i) calculating a non-alcoholic fatty liver disease (NFD) score from the patient's age, body mass index (BMI), aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ratio, platelet count, and hyperglycemic status; and (ii) calculating a non-alcoholic steatohepatitis score (NIS4) for the patient based on the levels of hsa-miR-34a-5p, alpha-2-macroglobulin (A2M), YKL-40, and glycosylated hemoglobin (HbA1c), measured in a blood sample or blood derivative from the patient; and determining the presence or absence of NAS risk in the patient based on these scores. where the NFS test is implemented before or after the NIS4 test.

The present invention relates to the technical field of immunotherapy, and in particular to adoptive T cell therapy or T cell receptor (TCR) gene therapy. The present invention provides a nucleic acid encoding at least one TCRα or β chain construct of a TCR construct, the TCR construct being capable of specifically binding to the MYD88L265P peptide of SEQ ID NO:2 in the presence of HLA-B*07:02 having a high affinity for the peptide / HLA complex. The present invention also provides the corresponding protein and host cell of the above nucleic acid, preferably CD8+ T cells, as well as the medical uses of the nucleic acid, protein or host cell, particularly in the diagnosis, prevention and / or treatment of cancers expressing MYD88L265P, such as non-Hodgkin B cell lymphomas selected from diffuse large B cell lymphoma (DLBCL) (such as activated B cell type DLBCL (ABC-DLBCL) or primary CNS DLBCL, cutaneous DLBCL, leg type DLBCL or testicular DLBCL), lymphoplasmacytic lymphoma (LPL) (such as Waldenström macroglobulinemia (WM)) and IgM monoclonal gammopathy of undetermined significance (IgM MGUS).

The invention discloses a sugar chain marker combination for diagnosing macroglobulinemia of Fahrenheit and application of the sugar chain marker combination. The marker combination comprises the following N-sugar chains: cFA22, cFA2B, cFA2 (6) G1, cFA2 (3) G1, A2G2, cFA2B (3) G1, cFA2G2, cFA2BG2, A3G32 and aFA3G32. By analyzing the change of an N-carbohydrate chain on glycoprotein in blood, the invention finds that a specific N-carbohydrate chain marker combination has significant correlation with WM. The marker combination shows high sensitivity and high specificity in WM diagnosis, can realize rapid detection through a fluorescence labeling technology, has the non-invasive advantage, can be used for early discovery and accurate diagnosis, and is beneficial to improvement of the cure rate and survival rate of patients. In addition, discovery of the bisecting two-antenna N-carbohydrate chain combination provides a new potential therapeutic target for WM, and the bisecting two-antenna N-carbohydrate chain combination has important clinical application value.

Disclosed herein are adoptive T cell therapies or T cell receptor (TCR) gene therapies from the treatment of cancer. The therapies utilize a nucleic acid encoding at least one TCR alpha or beta chain construct of a TCR construct capable of specifically binding to a MYD88 L265P peptide of SEQ ID NO: 2 in the context of HLA-B*07:02 having a high avidity to said peptide / HLA complex. Proteins corresponding to said TCR constructs and host cells, preferably, CD8+ T cells, comprising the TCR constructs are described, as well as the medical use of such nucleic acids, proteins or host cells, in particular, in the diagnosis, prevention and / or treatment of a MyD88 L265P expressing cancer such as a non-Hodgkin B-cell lymphoma selected from the group comprising diffuse large B-cell lymphoma (DLBCL), e.g., activated B-cell-like DLBCL (ABC-DLBCL) or pCNS DLBCL, cutaneous DLBCL, leg-type DLBCL or testicular DLBCL; lymphoplasmacytic lymphoma (LPL), e.g., Waldenström macroglobulinemia (WM); and IgM monoclonal gammopathy (IgM MGUS).

The invention relates to a kit for determining the content of alpha2-macroglobulin in human blood and urine, the kit comprises a reagent R1 and a reagent R2, the reagent R1 comprises a buffer solution, an electrolyte, a surfactant, a turbidity increasing agent and a preservative, the reagent R2 comprises carboxylated polystyrene latex microspheres coated with alpha2-macroglobulin polyclonal antibody IgG, a stabilizer, a buffer solution, an electrolyte, a protective agent and a preservative. The kit realizes quantitative detection of the content of alpha2-macroglobulin in blood and urine through latex enhanced immunoturbidimetry. By optimizing the particle size of latex microspheres, an antibody coating process and reaction system parameters, the detection sensitivity and stability are remarkably improved. The kit can be used for simultaneously determining the content of alpha2-macroglobulin in blood and urine, has a wide linear range (300-5000mg / L of blood and 2-100mg / L of urine), has sensitivity of 0.03 delta A / mg / L and repeatability CV of less than 5%, and is suitable for clinical rapid diagnosis.

Disclosed herein are methods for determining whether a subject is suffering from Waldenström macroglobulinemia (WM) or a precursor condition thereof, or multiple myeloma (MM) or a precursor condition thereof. These methods comprise determining, in a sample obtained from the subject, data indicative of the proportions of two or more immune cell populations. Methods of monitoring a subject with WM, or a precursor condition thereof, are also disclosed. These methods comprise determining in tumor cells obtained from a sample obtained from the subject and a reference sample expression of two or more gene expression signatures which indicate whether the subject is at risk of disease progression.

A pharmaceutical composition comprising α2-macroglobulin (A2M) and a serine protease protein such as porcine pancreatic elastase (PPE) is provided, wherein A2M and the serine protease protein such as PPE are bound as a protein complex, and this protein complex retains the CD95 protease cleavage activity and cancer cell killing activity of the serine protease, while sterically inhibiting the binding of the serine protease to fibrinogen and a serine protease inhibitor. Related methods of use and manufacturing for treating diseases such as cancer are also provided.

It is provided a method of diagnosing bladder cancer in a subject comprising measuring in a urine sample the protein level of expressions of at least two protein markers selected from complement factor H (CFH), Fibrinogen β (FGB), alpha-2-macroglobulin (A2M) and pancreatic alpha-amylase (AMY2A) and a kit for same. The method and kit allow to monitor and / or diagnose high-grade bladder cancer in patients suspected of having bladder cancer, having or not hematuria.