38 results about "CD74" patented technology

The present invention concerns CAR, CAR-T and CAR-NK constructs, preferably comprising a scFv antibody fragment against a disease-associated antigen or a hapten. More preferably, the antigen is a TAA, such as Trop-2. The constructs may be administered to a subject with a disease, such as cancer, autoimmune disease, or immune dysfunction disease, to induce an immune response against disease-associated cells. Where the constructs bind to a hapten, the subject is first treated with a hapten-conjugated antibody that binds to a disease associated antigen. Therapy may be supplemented by other treatments, such as debulking procedures (e.g., surgery, chemotherapy, radiation therapy) or coadministration of other agents. More preferably, administration of the construct is preceded by predosing with an unconjugated antibody that binds to the same disease-associated antigen. Most preferably, an antibody against CD74 or HLA-DR is administered to reduce systemic immunotoxicity induced by the constructs.

The present invention concerns methods and compositions for forming anti-cancer vaccine complexes. In preferred embodiments, the anti-cancer vaccine complex comprises an antibody moiety that binds to dendritic cells, such as an anti-CD74 antibody or antigen-binding fragment thereof, attached to an AD (anchoring domain) moiety and a xenoantigen, such as CD20, attached to a DDD (dimerization and docking domain) moiety, wherein two copies of the DDD moiety form a dimer that binds to the AD moiety, resulting in the formation of the vaccine complex. The anti-cancer vaccine complex is capable of inducing an immune response against xenoantigen expressing cancer cells, such as CD138negCD20+ MM stem cells, and inducing apoptosis of and inhibiting the growth of or eliminating the cancer cells.

The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an antibody or antigen-binding antibody fragment. The antibody may bind to EGP-1 ROP-2), CEACAM5, CEACAM6, CD74, CD19, CD20, CD22, CSAp, HLA-DR, AFP or MUC5ac and the immunoconjugate may be administered at a dosage of between 4 mg / kg and 24 mg / kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg / kg. When administered at specified dosages and schedules, the immunoconjugate can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy.

The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an antibody or antigen-binding antibody fragment. The antibody may bind to EGP-1 (TROP-2), CEACAM5, CEACAM6, CD74, CD19, CD20, CD22, CSAp, HLA-DR, AFP or MUC5ac and the immunoconjugate may be administered at a dosage of between 4 mg / kg and 24 mg / kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg / kg. When administered at specified dosages and schedules, the immunoconjugate can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy.

The present invention relates to therapeutic immunoconjugates comprising SN-38 attached to an antibody or antigen-binding antibody fragment. The antibody may bind to EGP-1 (TROP-2), CEACAM5, CEACAM6, CD74, CD19, CD20, CD22, CSAp, HLA-DR, AFP or MUC5ac and the immunoconjugate may be administered at a dosage of between 4 mg / kg and 24 mg / kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg / kg. When administered at specified dosages and schedules, the immunoconjugate can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy.

The present invention concerns methods and compositions for forming anti-cancer vaccine complexes. In preferred embodiments, the anti-cancer vaccine complex comprises an antibody moiety that binds to dendritic cells, such as an anti-CD74 antibody or antigen-binding fragment thereof, attached to an AD (anchoring domain) moiety and a xenoantigen, such as CD20, attached to a DDD (dimerization and docking domain) moiety, wherein two copies of the DDD moiety form a dimer that binds to the AD moiety, resulting in the formation of the vaccine complex. The anti-cancer vaccine complex is capable of inducing an immune response against xenoantigen expressing cancer cells, such as CD138negCD20+ MM stem cells, and inducing apoptosis of and inhibiting the growth of or eliminating the cancer cells.

In accordance with the invention, a novel gene translocation, (5q32, 6q22), in human non-small cell lung carcinoma (NSCLC) that results in a fusion proteins combining part of CD74 with Proto-oncogene Tyrosine Protein Kinase ROS Precursor (ROS) kinase has now been identified. The CD74-ROS fusion protein is anticipated to drive the proliferation and survival of a subgroup of NSCLC tumors. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ROS kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of the new fusion protein enables new methods for determining the presence of these mutant ROS kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.

The invention provides the identification of the presence of polypeptides with ROS kinase activity in mammalian lung cancer. In some embodiments, the polypeptide with ROS kinase activity is the result of a fusion between a ROS-encoding polynucleotide and a polynucleotide encoding a second (non-ROS) polypeptide. Three different fusion partners of ROS are described, namely proteins encoded by the FIG gene, the SLC34A2 gene, and the CD74 gene. The invention enables new methods for determining the presence of a polypeptide with ROS kinase activity in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer (e.g., an lung cancer).

The invention provides a cosmetic or therapeutic method for combating canities and / or stimulating natural pigmentation and / or treating a pigmentation disorder comprising administering at least one polynucleotide fragment comprising 18 consecutive nucleotides, the sequence of which corresponds to all or part of a gene on human chromosome 3 selected from KIAA 042, CCK, CACNA1D, ARHGEF3 and AL133097 genes, or the sequence of which corresponds to all or part of a gene on human chromosome 5 selected from the KLHL3, HNRPA0, CDC25C, EGR1, C5orf6, C5orf7, LOC51308, ETF1, HSPA9B, PCDHA1 to PCDHA13, CSF1R, RPL7, PDGFRB, TCOF1, AL133039, CD74, RPS14, NDST1, G3BP, GLRA1, C5orf3, MFAP3, GALNT10 and FLJ 117151 genes, or the sequence of which corresponds to all or part of a gene on human chromosome 11 selected from the GUCY1A2, CUL5, ACAT1, NPAT, ATM, AF035326, AF035327, AF035328, BC029536, FLJ20535, DRD2, ENS303941, IGSF4, LOC51092, BC010946, TAGLN, PCSK7 and ENS300650 genes, and diagnostic methods employing same.

The present invention belongs to the field of immunology and biotechnology, and provides an ELISA test kit of human-derived soluble CD74 protein and a detection method thereof. The kit of the present invention can accurately detect the content of human-derived soluble CD74 protein in body fluid or cell supernatant, and results are quantitatively analyzed by an enzyme-labeling instrument to exclude subjectivity of semi-quantitative methods such as immunohistochemistry, immunofluorescence, Western blot and the like; the kit has high sensitivity, the detected content of CD74 protein is as low as 800 pg / ml; according to the invention, no complicated instrument is necessary in detection; the kit is suitable for popularization and application in scientific research institutions and medical institutions, is suitable for large-scale detection of clinical samples, and can rapidly obtain massive data and information related to human-derived CD74 protein.

The present invention relates to methods of cancer therapy using subcutaneous administration of antibody-drug conjugates (ADCs). Preferably, the ADC comprises an antibody that binds to Trop-2, CEACAM5, CEACAM6, CD20, CD22, CD30, CD46, CD74, Her-2, folate receptor, or HLA-DR. More preferably, the drug is SN-38. Subcutaneous administration is at least as effective as intravenous administration of the same ADC. Surprisingly, subcutaneous administration can be used without inducing unmanageable adverse local toxicity at the injection site. Subcutaneous administration is advantageous in requiring less frequent administration, substantially reducing the amount of time required for intravenous administration, and reducing the levels of systemic toxicities observed with intravenous administration. When administered at specified dosages and schedules, the ADCs can reduce solid tumors in size, reduce or eliminate metastases and are effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy.

The present invention relates to methods of cancer therapy using subcutaneous administration of antibody-drug conjugates (ADCs). Preferably, the ADC comprises an antibody that binds to Trop-2, CEACAM5, CEACAM6, CD20, CD22, CD30, CD46, CD74, Her-2, folate receptor, or HLA-DR. More preferably, the drug is SN-38. Subcutaneous administration is at least as effective as intravenous administration of the same ADC. Surprisingly, subcutaneous administration can be used without inducing unmanageable adverse local toxicity at the injection site. Subcutaneous administration is advantageous in requiring less frequent administration, substantially reducing the amount of time required for intravenous administration, and reducing the levels of systemic toxicities observed with intravenous administration. When administered at specified dosages and schedules, the ADCs can reduce solid tumors in size, reduce or eliminate metastases and are effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy.

The invention provides anti-HLA-DQ2.5 / 8 antibodies and methods of using the same. The antibodies of the present invention have binding activity to human HLA-DQ2.5 / 8 and monkey MHC-DQ, but substantially no binding activity to HLA-DR, HLA-DP, or a complex of the invariant chain (CD74) and HLA-DQ2.5 / 8. The antibodies bind to HLA-DQ2.5 / 8 in the presence of a gluten peptide such as gliadin, i.e., bind to HLA-DQ2.5 / 8 forming a complex with the gluten peptide. The antibodies have neutralizing activity against the binding between HLA-DQ2.5 / 8 and TCR, and thus block the interaction between HLA-DQ2.5 / 8 and an HLA-DQ2.5 / 8-restricted CD4+ T cell. The antibodies do not undergo rapid internalization mediated by the invariant chain. These characteristics are particularly useful for treating celiac disease. Thus, the present invention also provides a method of treating celiac disease using the antibodies of the present invention.

The invention discloses a kit for quantitatively detecting ALK, RET and ROS1 fusion genes based on ddPCR. The kit comprises a negative reference substance, a positive reference substance, a PCR reaction solution I and a PCR reaction solution II. The invention provides an RT-PCR quantitative detection system based on ddPCR. The RT-PCR quantitative detection system comprises a forward primer, a reverse primer and a fluorescent probe, wherein the forward primer and the reverse primer aim at fusion genes EML4-ALK, CCDC6-RET and CD74-ROS1 and an internal control gene TBP. According to the kit, a forward primer is designed on a 5'partner gene, a probe and a reverse primer are designed on a 3'driver gene to detect ALK, RET and ROS1 fusion genes, and a detection result is expressed by a copy number in unit volume. Through adoption of a ddPCR detection method, whether EML4-ALK, CCDC6-RET and CD74-ROS1 fusion occurs in a clinical sample can be simply and rapidly detected, an important basis is provided for diagnosis, typing, clinical treatment and prognosis of ALK, RET and ROS1 related tumor diseases, and a new thought is provided for clinical treatment.

The invention belongs to the technical field of gene vaccines and particularly relates to a vibrio mimicus oral target epitope gene vaccine. The vibrio mimicus oral target epitope gene vaccine comprises the following steps: S1, designing a vaccine target gene OVepis; S2, inserting the vaccine target gene OVepis designed in the S1 into 261-280bp of a related peptide fragment area of a II-type molecule in a protein coding gene CD74 of an immune carrier grass carp, wherein the direction is from 5'end to 3'end of a sequence; forming a CD74(1-261bp)-Ovepis-CD74(280-711bp) mosaic gene of 1020 bp, loading the mosaic gene by using a freeze-drying bacterial ghost of escherichia coli DH5a of a targeted delivery vector, and obtaining the target epitope gene vaccine. The nucleotide sequence of the mosaic gene is shown in SEQ ID NO:20. The vibrio mimicus oral target epitope gene vaccine has the beneficial effects that: the oral target epitope gene vaccine not only prevents the degradation of nuclease in vivo and increases the expression of a DNA encoding gene of the vaccine in a local antigen presenting cell of a mucous membrane, but also efficiently transfers an expressed and processed antigenpeptide to cells T and B, so that the immune effect of the vaccine is greatly improved.

The antibodies of the present invention have specific binding activity to HLA-DQ2.5 and may have binding activity to HLA-DQ2.2 and / or HLA-DQ7.5, but substantially no binding activity to HLA-DQ8, HLA-DQ5.1, HLA-DQ6.3, HLA-DQ7.3, HLA-DR, HLA-DP, or a complex of the invariant chain (CD74) and HLA-DQ2.5. The antibodies bind to HLA-DQ2.5 in the presence of a gluten peptide such as gliadin, i.e., bind to HLA-DQ2.5 forming a complex with the gluten peptide. The antibodies have neutralizing activity against the binding between HLA-DQ2.5 and TCR, and thus block the interaction between HLA-DQ2.5 and anHLA-DQ2.5-restricted CD4+ T cell. The antibodies do not undergo rapid internalization mediated by the invariant chain.

In accordance with the invention, a novel gene translocation, (5q32, 6q22), in human non-small cell lung carcinoma (NSCLC) that results in a fusion proteins combining part of CD74 with Proto-oncogene Tyrosine Protein Kinase ROS Precursor (ROS) kinase has now been identified. The CD74-ROS fusion protein is anticipated to drive the proliferation and survival of a subgroup of NSCLC tumors. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ROS kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides; The disclosed identification of the new fusion protein enables new methods for determining the presence of these mutant ROS kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.

The invention discloses an application of a CD74 protein in preparation of a kit for identifying macrophage subsets in brains after ischemic injury. An inventor of the invention finds for the first time that the CD74 protein can distinguish macrophages into two subsets: CD74hi and CD74medium. The application is beneficial to further research on the functions of macrophages in ischemic brain tissues.

The invention provides an ELISA detection kit for mice-derived soluble CD74 proteins and a detection method of the ELISA detection kit, belonging to the technical field of immunology and biology. The kit can accurately detect the content of soluble CD74 proteins in mice body fluid, and a detection result is qualitatively analyzed by ELISA, so that the subjectivity of semiquantitative methods such as immunohistochemistry, immunofluorescence and western blot can be eliminated; moreover, the sensitivity is high, and the detected minimum content of the CD74 proteins can reach 781.25 pg / ml. No complicated instrument is needed in the detection, the ELISA detection kit and the detection method are easy to popularize and use in scientific research institutions and universities and medical institutions, basic research biological specimens can be detected on large scale, and a great amount of data and information related to the mice CD74 proteins can be rapidly acquired.

A method for detecting gene fusion that is a mutation responsible for cancer (driver mutation), wherein the method includes a step for detecting, in an isolated sample derived from a subject having cancer, any fusion polynucleotide among an EZR-ERBB4 fusion polynucleotide, KIAA1468-RET fusion polynucleotide, TRIM24-BRAF fusion polynucleotide, CD74-NRG1 fusion polynucleotide, or SLC3A2-NRG1 fusion polynucleotide, or a polypeptide encoded thereby.

The invention belongs to the technical field of gene rearrangement standard substances, and provides a CD74-ROS1 rearrangement DNA (deoxyribonucleic acid) standard substance for molecular diagnosis, an RNA (ribonucleic acid) standard substance for molecular diagnosis and application of the CD74-ROS1 rearrangement DNA standard substance and the RNA standard substance. The scheme provided by the invention comprises the following steps: constructing sgRNA of a No.6 intron aiming at a CD74 gene onto a vector pX330 to obtain a plasmid C4, constructing sgRNA of a No.33 intron aiming at an ROS1 gene onto the vector pX330 to obtain a plasmid R3, jointly transfecting a host cell with the plasmid C4 and the plasmid R3 to obtain a recombinant cell, and carrying out monoclonal treatment on the recombinant cell to obtain a cell for preparing a DNA standard substance or an RNA standard substance so as to obtain the DNA standard substance and the RNA standard substance. According to the CD74-ROS1 rearrangement standard substance sequence and cell provided by the invention, a sample can be stably provided for a long time, and the CD74-ROS1 rearrangement standard substance sequence and cell are very suitable for performance evaluation and long-term quality control requirements of LDT or IVD development.

The antibodies of the present invention have specific binding activity to HLA-DQ2.5 and may have binding activity to HLA-DQ2.2 and / or HLA-DQ7.5, but substantially no binding activity to HLA-DQ8, HLA-DQ5.1, HLA-DQ6.3, HLA-DQ7.3, HLA-DR, HLA-DP, or a complex of the invariant chain (CD74) and HLA-DQ2.5. The antibodies bind to HLA-DQ2.5 in the presence of a gluten peptide such as gliadin, i.e., bind to HLA-DQ2.5 forming a complex with the gluten peptide. The antibodies have neutralizing activity against the binding between HLA-DQ2.5 and TCR, and thus block the interaction between HLA-DQ2.5 and an HLA-DQ2.5-restricted CD4+ T cell. The antibodies do not undergo rapid internalization mediated by the invariant chain.

The invention provides a lung cancer fusion gene nucleic acid detection quality control product based on a CRSIPR-Cas9 technology. The lung cancer fusion gene nucleic acid detection quality control product is used for comprehensively monitoring a fusion gene detection process. A preparation method comprises the following steps of: (1) constructing a monoclonal HBE cell strain with specific fusionsites of EML4-ALK and CD74-ROS1 fusion genes by utilizing a CRISPR-Cas9 knock-in technology; (2) constructing a mouse subcutaneous transplantation tumor model by combining the monoclonal HBE cell strain successfully edited in the step (1) with a control wild cell strain; killing the model mouse after the tumor grows to 1cm<3>, collecting tumor tissues, pretreating, fixing, and embedding with paraffin; and (3) constructing a case tissue slice microarray according to a certain mutation / wild ratio by using the tumor tissues collected in the step (2) to obtain lung cancer fusion gene nucleic aciddetection quality control products with different fusion frequencies. The quality control product prepared by the invention has high similarity with non-small cell lung cancer, can truly realize the whole process of lung cancer sample tissue from sampling to detection, and realizes comprehensive monitoring of fusion gene detection.

Multi-specific binding proteins that bind NKG2D receptor, CD 16, and a tumor- associated antigen selected from c-MET, KIT, F3, IGF1R, Lewis Y, MUC13, MUC4, MCAM, LRRC32, sialyl-Tn, gpA33, GD3, GM2, EPHA3, TNFRSF10A, TNFSF11, CD74, and PMEL are described, as well as pharmaceutical compositions and therapeutic methods useful for the treatment of cancer.

The present invention relates generally to methods for diagnosing the presence or the risk of development or the therapy control of spondyloarthritis (Spa), in particular, of ankylosing spondylitis (AS) and undifferentiated spondyloarthritis in a subject, in particular in mammals. In addition, the present invention relates to test kits for use in the diagnosis of the presence or the risk of development, or for the therapy control of Spa, like AS and undifferentiated spondyloarthritis, in a subject. In particular, the present invention relates to a method for diagnosing the presence or the risk of development, or for the therapy control of Spa, like AS and undifferentiated spondyloarthritis, in a subject analysing for the presence of autoantibodies against CD74 and / or IKBKB in a subject. The presence of autoantibodies against CD74 and / or IKBKB is indicative for the presence or the risk of development, or for the therapy control of Spa, like AS and undifferentiated spondyloarthritis. In particular, detection of the presence of autoantibodies against CD74 and / or IKBKB allows early diagnosis of Spa, in particular, AS and undifferentiated spondyloarthritis.

Compositions for and methods of stimulating a MHC I mediated immune response comprising stimulating MHC I endolysosomal cross presentation in dendritic cells. Stimulation MHC I endolysosomal cross presentation may comprise over-expression CD74 in dendritic cells and / or targeting antigens to the MHC I endolysosomal cross presentation pathway. Fusion proteins comprising an antigen or fragment thereof and a CD74 endolysosomal targeting sequence are also provided.

The present application provides inter alia a fusion protein comprising a polypeptide wherein the polypeptide consists of a fragment of invariant chain which is operably linked to an antigenic sequence and wherein the fragment of invariant chain consists of a portion of residues 17-97 of SEQ ID NO: 1, wherein the portion comprises at least 5 contiguous residues from residues 77-92 of SEQ ID NO: 1.

A method of predicting outcome in a subject with for example Her2+ (ERα−) breast cancer comprising: (a) determining a HTICs expression signature comprising determining an expression level of 2 or more HTICS biomarkers selected from Aurkb, Ccna2, Scrn1, Npy, Atp7b, Chaf1b, Ccnb1, Cldn8, Nrp1, Ccr2, C1qb, Cd74, Vcam1, Cd180, Itgb2, Cd72, St8sia4, Kif11, Plk1, Chek1, Mphosph6, Cora1a, Ccl5, Cd3e, Hcls1, Vav1, Plek, Arhgdib, Il2rg, Sash3, Lck, Il2rb, Cybb, Cd79b, Sell, Ccnd2, Tnfrsf1b, Rftn1, Rac2 and Ly86; and (b) calculating a signature score, the signature score comprising a sum of HTICs biomarker expression parameters; wherein a signature score greater than a selected cut-off or control signature score is indicative of a poor outcome (HTICS+) and a signature score less than a selected cut-off is indicative of a good outcome (HTICS−). The methods can be used to prognose outcome and / or select suitable treatment. Arrays and kits for use with the methods are also provided.