62 results about "CD70" patented technology

Provided herein are anti-idiotypic antibodies that specifically recognize anti-CD70 antibody portions, particularly anti-CD70 antibody portions present in recombinant receptors, including chimeric antigen receptors (CARs). The present disclosure further relates to the use of anti-idiotypic antibodies to specifically identify and / or select cells expressing such recombinant receptors, such as anti-CD70 CAR T cells. The present disclosure further relates to the use of anti-idiotypic antibodies to specifically activate such cells.

The disclosure provides anti-CD70 antibodies, antigen binding fragments thereof, chimeric antigen receptors (CARs) and engineered T cell receptors (TCRs) comprising an antigen binding molecule that specifically binds to CD70, polynucleotides encoding the same, and in vitro cells comprising the same. The polynucleotides, polypeptides, and in vitro cells described herein can be used in an engineered TCR and / or CAR T cell therapy for the treatment of a patient suffering from a cancer. In one embodiment, the polynucleotides, polypeptides, and in vitro cells described herein can be used for the treatment of multiple myeloma.

The invention relates to a CD19 and CD70 targeted double-target chimeric antigen receptor and application thereof, the CD19 and CD70 targeted double-target chimeric antigen receptor comprises an extracellular antigen binding domain, a hinge region, a transmembrane domain, an intracellular costimulatory domain and an intracellular signal transduction domain, and the extracellular antigen binding domain has specific binding ability to CD19 and CD70. The double-target chimeric antigen receptor structure has a treatment effect of targeting double antigens or single antigens, can be used for preparing immune effector cells targeting CD19 and CD70, and provides a treatment or improvement approach for diseases related to CD19 and CD70 double expression or CD19 / CD70 single expression.

The present invention provides a method for preparing and using a CD70-specific diagnostic-integrated molecular imaging probe, which comprises a tumor targeting group and a radionuclide, the tumor targeting group being selected from a CD70-specific nanobody or a CD70-specific nanobody fusion protein, the CD70-specific nanobody being B3 or B6 having the amino acid sequences set forth in SEQ ID NO. 1 and SEQ ID NO. 3, and the CD70-specific nanobody fusion protein being ABDB3 or ABDB6 having the amino acid sequences set forth in SEQ ID NO. 5 and SEQ ID NO. 7. The present invention achieves noninvasive visualization of human CD70 molecule expression and realizes noninvasive diagnosis of renal cell carcinoma. This probe has the advantages of simple preparation, low cost, high specificity, high stability, short imaging cycle, low radiation dose, and easy clinical translation.

Provided herein are T cell receptor (TCR) fusion proteins (TFPs) that contain a CD70-binding domain, T cells engineered to express one or more TFPs, antibodies that specifically bind to CD70, and methods of their use for the treatment of diseases, including cancer.

The application provides a construction method of a humanized keloid mouse model, comprising the following steps: BAC plasmid construction and preparation; superovulation of experimental mice and collection of zygotes; pronuclear microinjection of zygotes; post-injection embryo transplantation; genotype identification; breeding and genetic analysis; and verification of construction results of the humanized immune system by immunohistochemistry and immunofluorescence. In the application, peripheral blood mononuclear cells treated by sCD27 and skin around keloids (homologous cells and tissues) are transplanted into NSG-MHC-DKO immune-deficient mice with overexpression of CD70 genes, so that HLA rejection of different homologous immune cells and tissues can be avoided, the internal microenvironment of keloids and the interaction between the internal microenvironment and the immune system can be restored to the maximum extent, and the influence of immune factors on the occurrence and development of keloids can be realized in vitro. The application first discovers and verifies that the activation of the CD27-CD70 axis can promote the occurrence and development of keloids, and provides a suitable animal model for the research and development of anti-keloid drugs, especially immunotherapy.

The present invention relates to bi-, tri-, or oligospecific anti-TNFR1 fusion proteins, which are monovalent for TNFR1 and exhibit excellent productivity and strong conditional TNFR1 agonism. The invention also relates to bi-, tri-, or oligospecific anti-TNFR1 nanobody fusion proteins which display strong conditional TNFR1 agonism upon binding to cell surface or extracellular matrix antigens such as PD-L1 or CD70. The invention also relates to methods of producing such bi-, tri-, or oligospecific anti-TNFR1 nanobody fusion protein constructs, pharmaceutical compositions comprising the same, as well as their uses for treating cancer.

To provide an allogeneic tumor cell vaccine.SOLUTION: Provided is an allogeneic tumor cell vaccine, comprising: (1) a population of proliferation-incompetent, live, genetically engineered tumor cells expressing one or more tumor-specific antigens, the population comprising at least three stably expressed immunomodulatory molecules, at least three immunomodulatory molecules being OX40 ligand (OX40L), CD27 ligand (CD70), and CD28 ligand (CD28L) including CD80, CD86, or both, to induce one or more subpopulations of PBMCs to proliferate in response to the expressed immunomodulatory molecules and subsequently enter an effector phase to kill tumor cells, and the subpopulations of PBMC cells comprising one or more of T lymphocytes, natural killer (NK) cells, dendritic cells (DCs), or B lymphocytes; and (2) a pharmaceutically acceptable carrier.SELECTED DRAWING: None

Provided herein are CD70-targeted chimeric antigen receptors (CARs), genetically engineered cells such as T cells containing the same, and related methods and uses of the genetically engineered cells in allogeneic cell therapy. Also provided are T cells that are genetically engineered with a CAR, such as a CD70-targeted CAR, and are further genetically engineered by one or more strategies to reduce host immune recognition of the engineered T cells, such as by heterologous expression of one or more additional transgenes and by genetic disruption to reduce or eliminate expression or one or more endogenous protein. Also provided are methods of making and using the engineered T cells for cell therapy, including in connection with cancer immunotherapy comprising adoptive transfer of the engineered T cells.

The presently disclosed subject matter provides cells, compositions, and methods for enhancing immune responses to tumor antigens. These cells comprise a first antigen-recognizing receptor that targets CD70. These cells have improved activity and / or efficiency. The present invention also provides a method for reducing tumor burden in a subject with renal cell carcinoma, pancreatic cancer, or ovarian cancer, comprising administering to the subject an effective amount of cells comprising a TCR-like fusion molecule that targets CD70.

The invention relates to a CD70 and BCMA targeting dual-targeting chimeric antigen receptor and an application thereof. The CD70 and BCMA targeting dual-targeting chimeric antigen receptor has specific binding ability to CD70 and BCMA. The immune effector cell prepared on the basis of the double-targeting chimeric antigen receptor has the following advantages that the probability that tumor cells escape treatment by losing a single antigen is greatly reduced, and the targeting treatment effect is improved; a CD70 nano antibody sequence is used, so that the length of an insertion fragment is greatly shortened, and the development difficulty of a process end is reduced; and the polypeptide has excellent proliferation capacity, is beneficial to prolonging the in-vivo duration time, and plays a more remarkable anti-tumor role. The invention provides a treatment or improvement approach for diseases related to BCMA-CD70 expression.

Several embodiments of the methods and compositions disclosed herein relate to immune cells that are genetically edited, for example, using Crispr / Cas, to modulate, reduce or otherwise eliminate expression of one or more endogenous genes. In several embodiments, the edited cells are engineered to express a chimeric antigen receptor targeting a tumor antigen, for example CD19, ligands of the NKG2D receptor, CD70, and / or BCMA, among others. In several embodiments, the editing enhances one or more aspects of the efficacy of the immune cells in cellular immunotherapy including cytotoxicity (e.g., ADCC) and / or persistence.

The present invention pertains to the field of biological medicines and relates to a nanobody specifically binding to CD70 or an antigen-binding fragment thereof. Specifically, the nanobody or the antigen-binding fragment thereof comprises complementary determining regions CDR1, CDR2, and CDR3 in the amino acid sequence set forth in any one of SEQ ID NOs: 4, 7, 11, 14, and 18. The present invention further relates to a chimeric antigen receptor (CAR) comprising the nanobody or the antigen-binding fragment thereof, a nucleic acid molecule encoding the CAR, an immune cell expressing the CAR, and use of the CAR or the immune cell for preventing and / or treating CD70-related conditions.

The invention belongs to the field of biological medicine, and relates to a double-epitope chimeric antigen receptor specifically combined with CD70. Specifically, the chimeric antigen receptor comprises an extracellular antigen binding structural domain, a spacer region structural domain, a transmembrane structural domain and an intracellular signal transduction structural domain, the extracellular antigen binding structural domain comprises a first antigen binding structural domain targeting CD70 and a second antigen binding structural domain targeting CD70, and the intracellular signal transduction structural domain comprises a first antigen binding structural domain targeting CD70 and a second antigen binding structural domain targeting CD70. The first antigen binding domain and the second antigen binding domain target different epitopes of CD70, and the first antigen binding domain and the second antigen binding domain are nano antibodies or antigen binding fragments thereof. The invention also relates to nucleic acid molecules encoding such CARs, to immune cells expressing such CARs, and to the use of these CARs and immune cells for the prevention and / or treatment of CD70-related conditions.

Provided herein are CD70-binding proteins comprising a CD70-binding domain and a transmembrane domain, engineered immune cells comprising the CD70-binding proteins, and methods of making and using the same. Also provided herein are engineered immune cells e.g. CAR (chimeric antigen receptor) T cells for administration to patients to treat cancer (e.g., solid tumors and hematologic tumors) and other unwanted conditions. The cells are engineered to functionally express a first antigen binding molecule e.g. a CD70 CAR and a second antigen binding molecule e.g. a second CAR that binds a target molecule characteristic of the cancer or other disease or unwanted condition. The cells may be further engineered to reduce the functional expression level of one or more of TRAC, CD52 and CD70. Also provided are methods of making and using the engineered cells, compositions and kits comprising them, and methods of treating by administering them.

The present application relates to the technical field of multi-gene detection, and in particular to a set of capture probes for follicular lymphoma multi-gene detection, a kit and a detection analysis method ARID1A, ARID1B, ATM, ATP6V1B2, B2M, BCL10, BCL2, BCL6, BCL7A, BTG1, BTG2, BTK, CARD11, CCND3, CD58, CD70, CD79A, CD79B, CDK4, CDKN2A The capture probe set comprises capture probes for specifically binding to 74 follicular lymphoma related genes, and the capture probe set preferably comprises nucleotides with sequences as shown in SEQ ID NO. 1-937. The probe set of the present application can realize one-time detection of variation in the full exon region of 74 follicular lymphoma related genes in the sample to be detected in the same system, has high specificity, high average sequencing depth and wide coverage area.

CD70 binding proteins or ligands, particularly CD27 polypeptides, and particularly variant CD27 extracellular binding domain polypeptides, are provided wherein the CD27 amino acid sequence is altered. The CD27 polypeptides and / or domains thereof, particularly the extracellular binding domains thereof are useful in the diagnosis and treatment of various conditions, including in cancer and immunotherapuetics. The CD27 polypeptides and / or domains thereof, particularly the extracellular binding domains thereof may also be used in lymphoid cell-mediated, including T cell-mediated, therapy, in chimeric antigen receptor (CAR) therapy, and / or in therapy in combination with chemotherapeutics, radiation therapy, immune modulators, cancer vaccines, cancer antigens, or anti-cancer agents. Particular variant CD27 polypeptides, extracellular domains, and novel CAR constructs are provided.

The compositions and methods described herein relate to the use of a CRISPR / Cas9 system in combination with a CAR technology for improving the activity of anti-CD70 CAR-T cells. The engineered cells may comprise a genetic modification in one or more of the HLA-A, HLA-B, TRAC, CIITA, TGFBR2, or CD70 genes.

The disclosure is directed to methods and compositions for treating cancers characterized by cells comprising chimeric antigen receptors (CARs) that bind CD70 and T-cell engaging antibody molecules (TEAMs) that bind CD33, nucleic acid molecules encoding chimeric antigen receptors (CARs) that bind CD70 and / or TEAMs that bind CD33, and compositions and methods related thereto.

This article provides information on T cell receptor (TCR) fusion proteins (TFPs) containing a CD70 binding domain, T cells engineered to express one or more TFPs, antibodies that specifically bind to CD70, and methods of using them to treat diseases including cancer.

The present invention relates to combination therapies, in particular combination therapies for the treatment of myeloid malignancies. The combination therapies are particularly useful in methods for the treatment of acute myeloid leukemia (AML). The combination therapies comprise an antibody or antigen-binding fragment thereof that binds to CD70 and a BCL-2 inhibitor, preferably venetoclax or a pharmaceutically acceptable salt thereof.

The invention belongs to the field of biological medicine, and relates to a nano antibody specifically bound with CD70 or an antigen binding fragment thereof. Specifically, the nano antibody or the antigen binding fragment thereof comprises complementary determining regions CDR1, CDR2 and CDR3 in an amino acid sequence as shown in any one of SEQ ID NOs: 4, 7, 11, 14 and 18. The invention also relates to chimeric antigen receptors (CARs) comprising such nanoantibodies or antigen binding fragments thereof, nucleic acid molecules encoding such CARs, immune cells expressing such CARs, and the use of said CARs or immune cells for the prevention and / or treatment of CD70-related conditions.

This application relates to methods for treating patients with reduced sensitivity to BCL-2 inhibitors. An antibody or antigen-binding fragment thereof that binds to CD70 is provided for treating myeloid malignancies in human subjects resistant to BCL-2 inhibitor treatment, and a method for treating myeloid malignancies in a subject, the method comprising (a) selecting a human subject with myeloid malignancies who has reduced sensitivity to or is refractory to BCL-2 inhibitors; and (b) administering the CD70-binding antibody or antigen-binding fragment thereof to the subject. In some embodiments, the myeloid malignancy is acute myeloid leukemia (AML). In some embodiments, the CD70-binding antibody is Cusatuzumab. In some embodiments, the BCL-2 inhibitor is co-administered with the CD70-binding antibody or antigen-binding fragment thereof. In some embodiments, the BCL-2 inhibitor is Venetoc.

The present disclosure relates to DNA constructs encoding CD19-specific chimeric antigen receptors (CARs) and other recombinant proteins, such as CD70-binding proteins or CD70-specific CARs, as well as engineered immune cells (e.g., CD19-specific CAR T cells or CD19 / CD70 dual CAR T cells) comprising the DNA constructs, methods of making the same, and uses thereof in therapeutic applications.

A population of genetically engineered T cells, comprising a disrupted protein tyrosine phosphatase non-receptor type 2 (PTPN2) gene and optionally a disrupted TRAC gene, a disrupted β2M gene, and / or a disrupted CD70 gene. Also provided herein are methods for making such genetically engineered T cells and therapeutic uses thereof.

To provide acute myeloid leukemia antigen targets for chimeric receptors and methods of using same.SOLUTION: There is provided an isolated immunoresponsive cell comprising (a) a first chimeric receptor comprising an extracellular antigen-binding domain that binds to a first antigen, and (b) a second chimeric receptor comprising an extracellular antigen-binding domain that binds to a second antigen, wherein each antigen is selected from a group consisting of FLT3, CD33, CLEC12A, MS4A3, VSTM1, LAT2, MLC1, CD131, GAPT, PRAM1, SLC22A16, SLC17A9, SPNS3, ADGRE2, IL3RA, CD117, CD93, IL1RAP, CD244, CCR1, LILRB2, PIEZO1, CD38, EMB, MYADM, LILRA2, CD300LF, and CD70, and wherein the first antigen is different from the second antigen.SELECTED DRAWING: Figure 1

The present disclosure relates to CRISPR related systems and components for targeting, editing and / or modulating CD70 (Cluster of Differentiation 70) gene expression. The disclosure also relates to methods and uses thereof related to engineered cells comprising T cells or T cell precursors.

The application provides a monoclonal antibody targeting human CD70 and application thereof. Specifically, the application obtains a group of monoclonal antibodies targeting human CD70 from B cells of mice immunized by the application, the monoclonal antibodies have high affinity with CD70 protein on the surface of cells, and can block the interaction between CD27 protein and CD70 protein. In addition, the application also provides a fusion protein, CAR-T / NK / macrophage, immunoconjugate and the like containing the antibody, and the CAR-T cell has specific killing function to cells expressing CD70.