93 results about "CD70" patented technology

The invention provides a preparation method and application of a CD70 specific nano antibody molecular imaging probe. The probe comprises a tumor targeting group, radionuclide and a bifunctional chelating agent, the tumor targeting group is a CD70 specific nano antibody; the CD70 specific nano antibody is R8B4, and the amino acid sequence of the R8B4 is as shown in SEQ ID No. 1. The probe provided by the invention can realize noninvasive diagnosis of solid tumors such as renal clear cell carcinoma and malignant tumors of a blood system; reabsorption of the compound in the kidney is effectively inhibited through charge adjustment, kidney uptake is remarkably reduced, non-specific signals are reduced, the signal-to-noise ratio during targeted imaging or treatment is increased, and the imaging quality and treatment safety are improved. The probe not only has a wide application prospect in tumor diagnosis, but also provides a new technical support for targeted therapy and individualized precision medical treatment, and has important scientific research and clinical application values.

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.

The invention relates to combination and combination therapies, particularly for the treatment of a myeloid malignancy, such as acute myeloid leukemia (AML) or a myelodysplastic syndrome (MDS). The combination therapies include (i) a recombinant binding protein comprising (a) an ankyrin repeat domain specifically binding CD3 and (b) at least one, at least two, or at least three further ankyrin repeat domains, wherein each of the at least one, at least two, or at least three further ankyrin repeat domains specifically binds one tumor-associated antigen, suitably one selected from the group consisting of CD123, CD33 and CD70, and (ii) a Bcl-2 inhibitor, e.g., venetoclax, or a pharmaceutically acceptable salt thereof and / or (iii) a hypomethylating agent, e.g., azacitidine or decitabine.

The present invention relates to an anti-CD70 nanoantibody and a use thereof. The present invention provides a CD70 binding molecule, containing the anti-CD70 nanoantibody or an antigen binding fragment thereof. Complementarity-determining regions (CDRs) of the anti-CD70 nanoantibody comprise CDR1, CDR2 and CDR3. The present invention also provides a chimeric antigen receptors containing the CD70 binding molecule and an expression cell thereof. The antibody and the cell of the present disclosure have good safety and therapeutic effects targeting CD70.

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 present disclosure relates to DNA constructs encoding a CD19-specific chimeric antigen receptor (CAR) and other recombinant proteins, for example, a CD70-binding protein or a CD70-specific CAR, and 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.

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.

The present invention provides a CD70-specific nanoantibody, a molecular imaging probe, and a preparation method and application thereof. The probe includes a tumor-targeting group, a radionuclide, and a bifunctional chelator; the tumor-targeting group is a CD70-specific nanoantibody; the CD70-specific nanoantibody is RD06, and the amino acid sequence of RD06 is shown in SEQ ID No. 1. The probe of the present invention can achieve non-invasive diagnosis of solid tumors such as renal clear cell carcinoma and hematological malignancies; and through charge adjustment, it effectively inhibits its reabsorption in the kidney, significantly reduces renal uptake, reduces nonspecific signals, improves the signal-to-noise ratio during targeted imaging or treatment, and improves imaging quality and treatment safety. This probe not only has broad application prospects in tumor diagnosis, but also provides new technical support for targeted therapy and personalized precision medicine, and has important scientific research and clinical application value.

Aspects of the present disclosure include compositions and methods for treating tumors expressing CD70 with engineered γδ T cells. In some embodiments, the γδ-T cells comprise a chimeric antigen receptor (CAR) construct. The CAR construct can include the full-length CD27 receptor domain, a co-stimulatory domain, an intracellular signaling domain, combinations thereof, or all of them. The CAR construct can contain a domain encoding an additional polypeptide that confers advantageous functions to the γδ T cells.

The present application provides a bispecific antibody-NK cell conjugate that binds to CD16A molecules and CD70 molecules, a bispecific antibody that binds to CD16A molecules and CD70 molecules, a pharmaceutical composition comprising the bispecific antibody-NK cell conjugate or the bispecific antibody, and their uses.

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 present invention belongs to the field of cellular immune engineering technology, and in particular to a kind of 293T multi-target target cell and its preparation method and application.The target cell includes a nucleotide fragment a expressing antigen CEA, a nucleotide fragment b expressing antigen CD19, a nucleotide fragment c expressing antigen BCMA, and a nucleotide fragment d expressing antigen CD70. Its preparation method is to select a basic cell (293T cell), construct it by means of exogenous construction, and then detect its antigen expression by flow cytometry, and sort out target cells that simultaneously highly express antigens CEA, CD19, BCMA and CD70 as target cells. The target cell exogenously expresses multiple antigens that can be used for the detection of multiple targets, and the operation that needs to be repeated 4 times is condensed into an operation once, which reduces the workload of cell culture, greatly saves time and cost, and the background factor secretion amount is normal during detection, the factor detection result is stable, the signal-to-noise ratio is higher, and it is more conducive to the quality detection of subsequent products.

The presently disclosed subject matter provides cells, compositions and methods for enhancing immune responses toward tumor antigens. It relates to cells comprising a first antigen-recognizing receptor that targets CD70. These cells have improved activity and / or efficiency.

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.