117 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.

Several embodiments of the methods and compositions disclosed herein relate to immune cells that are gene edited (e.g., 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 chimeric antigen receptors that target tumor antigens (e.g., CD19, ligands of the NKG2D receptor, CD70, and / or BCMA, etc.). In several embodiments, the editing enhances one or more aspects of immune cell efficacy in cellular immunotherapy, including cytotoxicity (e.g., ADCC) and / or persistence.

Disclosed herein a polypeptides for use in chimeric antigen receptors (CARs) for binding to CD70-expressing cells. The polypeptides are variants of a natural ligand for CD70. CD70-targeting CARs demonstrate enhanced cytotoxic against CD70-positive cancer cells. The polypeptides may also be used to detect the presence of CD70-expressing cells that are implicated in disease.

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 combinations and methods using same for the treatment of malignancy, particularly a myeloid malignancy such as acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), chronic myeloid leukemia (CML), and chronic myelomonocytic leukemia (CMML). The combination may comprise an antibody or antigen-binding fragment thereof that binds to CD70, and an inhibitor of BCL-2. In certain embodiments, the antibody is ARGX-110 (cusatuzumab). In certain embodiments, the BCL-2 inhibitor is venetoclax. In certain embodiments, the combination provides synergistic treatment of AML. The combination may additionally comprise at least one additional anti-cancer agent.

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 invention relates to the technical field of biology, in particular to an anti-CD70 monoclonal antibody, a hybridoma cell strain and application thereof. The invention provides a monoclonal antibody. Amino acid sequences of three CDR regions of a heavy chain of the monoclonal antibody respectively have amino acid sequences shown as SEQ ID NO: 11, 12 and 13; the amino acid sequences of the three CDR regions of the light chain of the gene respectively have the amino acid sequences shown as SEQ ID NO: 6, 7 and 8. The anti-CD70 monoclonal antibody provided by the invention can specifically recognize a CD70 recombinant protein expressed by eukaryotic expression and a CD70 protein expressed on a cell membrane. The CD70 detection kit constructed by the anti-CD70 monoclonal antibody is high in sensitivity and good in specificity, and has a better application effect in various detections including enzyme-linked immunosorbent assay, flow cytometry, immunofluorescence and the like.

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 present disclosure relates to methods and compositions for treating cancer characterized by cells comprising a chimeric antigen receptor (CAR) that binds to CD70 and a T cell-engaging antibody molecule (TEAM) that binds to CD33; a nucleic acid molecule encoding a chimeric antigen receptor (CAR) that binds to CD70 and / or a TEAM that binds to CD33; and compositions and methods related thereto.

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.

Compositions and methods for editing, e.g., altering a DNA sequence, within a CD70 gene are provided. Compositions and methods for reducing or eliminating CD70 protein expression in a cell are provided. Compositions and methods for immunotherapy are provided.

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 generally relates to a combination of an mRNA molecule encoding a functional immunostimulatory protein and a CTLA4 pathway inhibitor. In particular, it relates to a combination of one or more mRNA molecules encoding at least one functional immunostimulatory protein selected from a list including CD40L, CD70 and caTLR4, and a CTLA4 pathway inhibitor, optionally also in the form of an mRNA molecule. The present invention also relates to a vaccine comprising such a combination, and the use of the combination and vaccine of the present invention in human or veterinary medicine, in particular in the prevention and / or treatment of cell proliferative diseases.

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.