52 results about "CD22" patented technology

Provided herein are particles comprising polynucleotide constructs for generating cells expressing anti-CD22 chimeric antigen receptor, as well as vectors, such as lentiviral vectors, comprising same, cells comprising same, and methods of using same. Some embodiments include a surface-engineered lentiviral vector. In some embodiments, the lentiviral vector further encodes a synthetic receptor protein.

The invention provides compositions and methods for treating diseases associated with expression of CD20 or CD22. The invention also relates to chimeric antigen receptor (CAR) specific to CD20 or CD22, vectors encoding the same, and recombinant T or natural killer (NK) cells comprising the CD20 CAR or CD22 CAR. The invention also includes methods of administering a genetically modified T cell or NK cell expressing a CAR that comprises a CD20 or CD22 binding domain.

The invention relates to CD22 binding molecules and uses thereof. The invention provides a CD22 binding molecule which comprises an anti-CD22 nano antibody or an antigen binding fragment thereof, and a complementary determining region (CDR) of the anti-CD22 nano antibody comprises CDR1, CDR2 and CDR3.

The present disclosure provides compositions and methods for treating diseases associated with expression of CD19 and / or CD22, e.g., by administering a recombinant T cell or natural killer (NK) cell comprising a CD22 CAR and a CD19 CAR as described herein. The disclosure also relates to CAR molecules specific to CD22 and / or CD19, methods of making a cell comprising the same and vectors encoding the same.

This invention discloses an immune cell that secretes type 2 cytokines under hypoxic conditions and its applications, belonging to the fields of genetic engineering and cell engineering. The invention first constructs a nucleotide fragment encoding hypoxia-induced type 2 cytokines, including a signal peptide gene sequence, a CAR molecule nucleotide sequence targeting CD19 and CD22, and an IL-4 or IL-10 nucleotide sequence containing multiple HRE motifs of a hypoxia-inducible promoter. This nucleotide fragment is delivered to immune cells for stable expression, yielding an immune cell that secretes type 2 cytokines under hypoxic conditions. This immune cell secretes IL-4 or IL-10 only under hypoxic conditions, thereby leveraging the metabolic reprogramming effect of IL-4 or IL-10 on immune cells to enhance their activity under hypoxic conditions, thus achieving better long-term anti-tumor effects.

Provided is a bispecific chimeric antigen receptor targeting CD19 and CD22, which comprises extracellular antigen binding domains of heavy-chain variable regions and light-chain variable regions of anti-CD19 and anti-CD22 antibodies. Further provided is a bispecific CAR-T cell targeting CD19 and CD22.

The invention belongs to the technical field of biological medicines, and particularly relates to an anti-CD22 nano antibody as well as a preparation method and application thereof. The anti-CD22 nano antibody comprises a framework region and a complementarity determining region, wherein the complementarity determining region comprises CDR1 (SEQ ID NO: 1), CDR2 (SEQ ID NO: 2) and CDR3 (SEQ ID NO: 3). The preparation method comprises the following steps: immunizing alpaca by using Human CD22 / His protein, extracting RNA (Ribonucleic Acid) from PBMC (Peripheral Blood Mononuclear Cell) and reversely transcribing into cDNA (Complementary Deoxyribose Nucleic Acid), constructing a phage display library, then performing CD22 antigen protein elutriation to obtain positive clone, and after sequencing analysis, expressing the antibody by using a mammalian cell expression system. The optimized phage display technology is adopted, the screening period is short, and the obtained nano antibody is small in molecular weight, stable in structure and high in affinity to CD22. The antibody can be efficiently expressed through mammalian cells, and natural modification activity is reserved.

The present invention relates to NK cells expressing dual-targeting chimeric antigen receptors for CD19 and CD22, and uses thereof. In the present invention, it was found that the delivery efficiency of a CAR expression vector and the production efficiency of CAR-NK cells are excellent when, among the cell surface proteins of PBMCs for producing CAR-NK cells (UCI-101), CD16 is expressed at 70% or less, natural killer group 2D (NKG2D) is expressed at less than 10%, CD57 is expressed at 30% or less, low-density lipoprotein receptor (LDLR) is expressed at 0.1% or more, and natural cytotoxicity triggering receptor 3 (NKp30) is expressed at less than 10%. In addition, optimal conditions for inducing NK cell differentiation and optimal conditions for transduction, under which the delivery efficiency of a CAR expression vector and the production efficiency of CAR-NK cells are excellent, were established, and CAR-NK cells produced by the method according to the present invention were found to exhibit an excellent antitumor effect in an animal model, and thus can be effectively used as a composition for preventing or treating diseases related to CD22 (or CD19) expression or diseases related to B cells.

This provides immune response-inducing molecules that have affinity for cancer-related therapeutic targets. [Solution] Anti-CD22 single-domain antibodies (sdAbs) prepared by immunizing llamas with the extracellular domain of a dominant human CD22 isoform are provided. Also provided are multivalent antibodies containing any one of the sdAbs, such as bispecific T-cell engagers, bispecific killer cell engagers (BiKEs), and triplicate killer cell engagers (TriKEs). Furthermore, chimeric antigen receptors (CARs) for CAR-T therapy containing any one of the aforementioned sdAbs are described. The use of these molecules in the treatment of cancer is also provided.

The application provides chimeric antigen receptors (CARs) that target cluster of differentiation 19 (CD 19) and / or cluster of differentiation 22 (CD22), and their uses in tumor immunotherapy. The application also provides polynucleotides and vectors that encode the CARs, as well as host cells comprising the CARs. The application also provides methods for preparing host cells comprising the CARs and methods for treating patients using the modified host cells.

The present disclosure relates to CD19 / 22 CAR T-cell products and methods for treating high risk or relapsed CD19+ or CD22+ haematological malignancies.

The present invention is directed to the field of immunotherapy, in particular, adoptive T cell therapy or T cell receptor (TCR) gene therapy of cancer, in particular, of B cell lymphoma or B cell leukemia. The invention provides a nucleic acid encoding TCR alpha or beta chain constructs of TCR constructs capable of specifically binding to a peptide of SEQ ID NO: 1, derived from the lineage specific antigen CD22, in the context of HLA-A2 and to subsequently lyse CD22-positive cells. The invention further provides a corresponding protein and host cell. e.g., a CD8+ T cell, pharmaceutical compositions comprising the same, and therapeutic use for treatment of B cell lymphoma or B cell leukemia, such as diffuse large B-cell lymphoma (DLBCL).

The application belongs to the technical field of cell engineering, and particularly relates to a bispecific antibody targeting CD22 and CD19, a chimeric antigen receptor thereof and application. In the bispecific antibody, a CD22 light chain and a CD22 heavy chain are connected through a linker 4 to form a CD22 single-chain antibody, and a CD19 light chain and a CD19 heavy chain are connected through a linker 4 to form a CD19 single-chain antibody, which comprises one of the following structures: (1) the CD22 single-chain antibody and the CD19 single-chain antibody are connected through a linker 1 or a liner 2; (2) the two ends of the CD19 single-chain antibody are connected with the CD22 light chain and the CD22 heavy chain through a linker 3, respectively. The chimeric antigen receptor provided by the application can simultaneously target two different tumor antigens, improve the killing of tumor cells, reduce the probability of immune escape, and reduce the tumor recurrence rate after CAR-T treatment.

The present disclosure relates generally to immunoglobulin-related compositions (e.g., antibodies or antigen binding fragments thereof) that can bind to the CD22 protein. The antibodies of the present technology are useful in methods for detecting and treating a CD22-associated cancer, a CD22-associated autoimmune disease, or a CD22-associated allergy in a subject in need thereof.

Chimeric antigen receptors containing CD19 / CD22 or CD22 / CD19 antigen binding domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.

The application belongs to the technical field of biological medicine, and particularly relates to an anti-CD22 nanobody and a preparation method and application thereof. The anti-CD22 nanobody comprises a framework region and a complementarity determining region, wherein the complementarity determining region comprises CDR1 (SEQ ID NO: 1), CDR2 (SEQ ID NO: 2) and CDR3 (SEQ ID NO: 3). The preparation method comprises the following steps: immunizing a llama with a Human CD22 / His protein, extracting RNA from PBMC cells and reverse transcribing the RNA into cDNA, constructing a phage display library, obtaining a positive clone through CD22 antigen protein panning after sequencing analysis, and expressing the antibody through a mammalian cell expression system. The application adopts an optimized phage display technology, has a short screening cycle, and the obtained nanobody has a small molecular weight, a stable structure and high affinity to CD22. The antibody can be efficiently expressed through a mammalian cell, and retains natural modification activity.

The present disclosure relates to an antibody binding to CD22, a bispecific antibody including the same, a chimeric antigen receptor, an antibody-drug conjugate, and uses thereof. According to one aspect, effective anticancer effects can be provided even for patients who are refractory to CD19-targeted therapies. Further, when using CD22 CAR NK cells or bispecific CD22 / CD19 CAR NK cells, significantly enhanced reduction of cancer cells can be achieved.

The present invention provides a cell that co-expresses a first chimeric antigen receptor (CAR) and a second CAR on the cell surface, each CAR comprising an antigen binding domain, wherein the antigen binding domain of the first CAR binds CD19 and the antigen binding domain of the second CAR binds CD22.

The invention belongs to the technical field of biomedicine, and relates to a biomarker for diagnosing blood stasis syndrome of ischemic heart failure and application of the biomarker. The biomarker for diagnosing the blood stasis syndrome of the ischemic heart failure, provided by the invention, is at least one of a gene marker and a protein marker; wherein the gene marker is at least one of CD19, CD22, CD79A, CD79B and CR2, and the gene marker is at least one of CD19, CD22, CD79A, CD79B and CR2; the protein marker is at least one of F2, F8, F9 and FN1. The invention also provides a product for diagnosing the blood stasis syndrome of the ischemic heart failure. The kit contains a reagent for detecting the gene marker or / and the protein marker. By detecting the expression level of the biomarker in the blood of a patient with the ischemic heart failure blood stasis syndrome, the patient with the ischemic heart failure blood stasis syndrome and a healthy control can be effectively diagnosed and distinguished, and auxiliary diagnosis of the ischemic heart failure blood stasis syndrome is achieved.

The present invention provides a bispecific chimeric antigen receptor that targets CD19 and CD22, which comprises an extracellular antigen-binding domain comprising the heavy chain variable region and the light chain variable region of an anti-CD19 antibody and an anti-CD22 antibody.The present invention further provides a bispecific CAR-T cell that targets CD19 and CD22.

The application discloses a functionalized sialic acid compound and a preparation method and application thereof, and has a structural formula: after being taken by tumor cells, the application is catalyzed by esterase and carboxypeptidase highly expressed in tumors, and butyric acid and PBA-Sia are released respectively; wherein, butyric acid, as a known tumor growth inhibitor, can play a role by regulating the cell cycle and inducing cell apoptosis; butyric acid has an inhibiting effect on various tumors; PBA-Sia, which is a high-binding force ligand of a B cell membrane protein CD22 site introduced to the surface of cancer cells through sugar metabolism, can enhance the recognition and attack ability of B immune cells to tumors; PBA-Sia on the surface of cancer cells and butyric acid released in cells synergistically inhibit tumor cell proliferation.

Provided herein are particles comprising polynucleotide constructs for generating cells expressing anti-CD22 chimeric antigen receptor, as well as vectors, such as lentiviral vectors, comprising same, cells comprising same, and methods of using same. Some embodiments include a surface-engineered lentiviral vector. In some embodiments, the lentiviral vector further encodes a synthetic receptor protein.

The present disclosure provides multispecific anti-CD22 / anti-4-1BB antigen-binding molecules comprising a first antigen-binding domain that binds specifically to CD22 and a second antigen-binding domain that binds specifically to 4-1 BB. In certain embodiments, the molecules further comprise a third antigen-binding domain that binds 4-1 BB. In certain embodiments, the molecules are multispecific antibodies or antigen-binding fragments thereof. In certain embodiments, the antibodies are useful in treating a CD22-associated disease or disorder (e.g., lymphoma).

The present invention provides a cell that co-expresses a first chimeric antigen receptor (CAR) and a second CAR on the surface of the cell, each CAR comprising an antigen binding domain wherein the antigen binding domain of the first CAR binds CD19 and the antigen binding domain of the second CAR binds CD22.

The present application relates to the use of an Axl agonist, a Mertk agonist, a CCR5 inhibitor or a CD22 inhibitor in the prevention or treatment of severe acute pancreatitis (SAP).

The present invention provides anti-CD22 antibody molecules and CD22-targeting chimeric antigen receptors (CARs) constructed using the anti-CD22 antibody molecules. The present invention further provides applications of the anti-CD22 antibody molecules and the chimeric antigen receptors in the production of medicines for treating CD22-associated diseases.

The present invention discloses a dual-targeted CAR-T cell based on a shark VNAR single-domain antibody and a preparation method thereof. First, a high-affinity CD19 / CD22-specific VNAR single-domain antibody is obtained by immunizing sharks, and then a CAR molecule containing a dual VNAR tandem structure is constructed, and the CD8α hinge region, CD28 transmembrane region and 4-1BB-CD3ζ intracellular signaling domain are integrated. The CAR-T cell significantly reduces off-target killing of normal B cells while maintaining efficient killing of double-positive tumor cells. Experiments have shown that its IL-6 release is reduced by 68.8%, which can reduce the risk of cytokine storm and provide a highly specific solution for the treatment of B-cell malignancies.

The present invention provides therapeutics for the treatment of CD22-positive cancers such as B-cell acute lymphoblastic leukemia (B-ALL). In particular, the present invention provides an anti-CD22 monoclonal antibody whose scFv as a part of chimeric antigen receptors (CAR) T-cells can target the fcst Ig extracellular domain of the CD22 antigen, the farthest domain from the membrane, for use in the treatment of CD22-positive cancers.

The invention relates to a tissue marker for proton radiation heart injury and application of the tissue marker. The tissue marker comprises one or more of a transcription marker and a protein marker. Wherein the transcription marker comprises one or more of PIK3R5, CCR7, IL7R, CD7, CD22, CR2, CCL5 and VAV1, and the transcription marker comprises one or more of PIK3R5, CCR7, IL7R, CD7, CD22, CR2, CCL5 and VAV1; and the protein marker comprises one or more of SIRT1 and HMGB1 (High Mobility Group Box 1). According to the invention, the differential marker is used as a potential biomarker of the radioactive heart loss, and a research method for researching the radioactive heart loss by using a mouse model is provided, so that a demonstrative research is provided for multi-omics analysis of the radioactive heart loss and explanation of an action mechanism of the radioactive heart loss.

The present disclosure provides multispecific anti-CD22 / anti-4-1BB antigen-binding molecules comprising a first antigen-binding domain that binds specifically to CD22 and a second antigen-binding domain that binds specifically to 4-1BB. In certain embodiments, the molecules further comprise a third antigen-binding domain that binds 4-1BB. In certain embodiments, the molecules are multispecific antibodies or antigen-binding fragments thereof. In certain embodiments, the antibodies are useful in treating a CD22-associated disease or disorder (e.g., lymphoma).