68 results about "CD30" patented technology

The present invention inter alia relates to a T-cell expressing a chimeric CD 95 receptor comprising a polypeptide, wherein said polypeptide comprises at least one CD 95-derived polypeptide region having at least 60% sequence identity with a polypeptide domain, a polypeptide region or a polypeptide motif of a human CD 95 wildtype receptor, wherein said human CD 95 polypeptide region comprises a CD 95 extracellular ligand binding domain; further wherein said polypeptide comprises at least one non-CD 95-derived co- stimulatory cytoplasmic polypeptide domain, region or motif of a tumor necrosis factor receptor superfamily protein comprising CD40, CD40L, CD27, HVEM, GITR, CD30, OX40, and / or LTBR, an immunoglobulin superfamily (IgSF) protein, a Toll-like-receptor, and / or an IL6-receptor family protein; wherein the T-cell further expresses an engineered T-cell receptor. The present invention also relates to a vector comprising nucleic acids encoding for the CD 95 receptor and the engineered T-cell receptor, as well as to a kit for preparing the T-cells of the present invention, and a pharmaceutical composition comprising the T-cells. The invention also relates to a method for preparing a T-cell for immunotherapy, and to a method for treating a patient having a disease comprising administering the pharmaceutical composition.

The invention discloses a bispecific antibody which comprises a first protein functional region targeting CD30 and a second protein functional region targeting CD16a, the first protein functional region comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises HCDR1, HCDR2 and HCDR3, and the light chain variable region comprises LCDR1, LCDR2 and LCDR3. The invention also discloses nucleic acid for coding the antibody, a recombinant expression vector, a transformant, a preparation method of the antibody, an antibody drug conjugate, a pharmaceutical composition or a kit containing the antibody drug conjugate, and applications of the nucleic acid, the recombinant expression vector and the transformant in preparation of drugs for preventing and / or treating tumors. The bispecific antibody provided by the invention can effectively activate the NK cells and can effectively target human tumor cell related antigen CD30 protein, mediate the killing activity of the NK cells to target cells, and induce and further enhance the tumor inhibition effect of the NK cells to tumor cells.

The present invention inter alia relates to a chimeric transmembrane receptor comprising a polypeptide, wherein the polypeptide comprises at least one T cell immunoreceptor with Ig and ITIM domains (TIGIT) polypeptide region comprising a TIGIT extracellular ligand binding domain; further wherein the polypeptide comprises at least one non-TIGIT polypeptide region, wherein the at least one non-TIGIT polypeptide region comprises a transmembrane polypeptide region of CD2, CD40, HVEM, or CD30, and wherein the at least one non-TIGIT polypeptide region comprises at least one costimulatory cytoplasmic polypeptide domain, region or motif of CD2, CD40, HVEM, or CD30, or wherein the transmembrane domain is from TIGIT and further wherein the at least one non-TIGIT polypeptide region comprises at least one costimulatory cytoplasmic polypeptide domain, region or motif of CD2 or CD28. The invention also relates to corresponding nucleic acids, vectors and T-cells comprising or expressing the chimeric receptors, to a pharmaceutical composition comprising the T-cells, and to methods for preparing a T-cell for immunotherapy and for treating a disease, respectively, wherein the chimeric transmembrane receptor is used.

The present invention provides novel antibodies and antigen binding fragments thereof that bind to human CD30. Also presented are single chain variable antibodies, chimeric antigen receptors and uses thereof. Methods of treating cancer are also disclosed.

The present application provides an anti-human CD153 monoclonal antibody that specifically binds to human CD153 and inhibits an intermolecular interaction between human CD153 and CD30, or a binding fragment thereof. The present application also provides: a chimeric antigen receptor including an extracellular antigen binding domain, a transmembrane domain, and an intracellular signaling domain, wherein the extracellular antigen binding domain has the same heavy-chain hypervariable region and the same light-chain hypervariable region as those in the monoclonal antibody according to the present application; and a CAR-T cell capable of expressing the chimeric antigen receptor. The monoclonal antibody and the binding fragment thereof and the CAR-T cell according to the present application are useful for the treatment or prevention of diseases associated with CD153, such as multiple sclerosis.

The present invention relates to third-generation CAR-CD30 T cells for the treatment of CD30+ tumors such as lymphoid malignancies, leukemias, and solid tumors.

The present disclosure provides a scalable and practical off-the-shelf allogeneic T cell therapy for treating cancer including employing a population of nonexhausted allogeneic virus specific CD4+ T cells, CD8+ T cells or CD4+ and CD8+ T cells that express a nonexhausted PD-1negTIGITnegTCF-1High TOXLo early stem cell TSCM phenotype. The virus-specific population of CD4+ T cells, CD8+ T cells or CD4+ and CD8+ T cells that expresses the nonexhausted early stem cell TSCM phenotype and comprises TCRs specific for a protein of a virus is genetically modified to stably express up to three chimeric antigen-receptors (CARs). Each CAR is specific for a cancer antigen. At least one of the CARs comprises a CD30 CAR expressing a CD30-specific scFv fragment, and / or a chimeric alloimmune defense receptor (ADR); and / or a chimeric HLA accessory receptor fused with a cytolytic endodomain of the T cell receptor zeta chain, thereby reducing risk of host versus graft rejection (HVGR). In some regimens, multiple populations of cells can be combined and co-infused as the off the shelf T cell therapies.

The invention provides an anti-CD30 rabbit Fab antibody as well as a preparation method and application thereof. Human CD30 protein is expressed through in-vitro recombination, a rabbit is immunized for three times by using the CD30 protein, peripheral blood lymphocytes are separated out, total RNA of the peripheral blood lymphocytes is extracted, the peripheral blood lymphocytes are reversely transcribed into cDNA, the cDNA is taken as a template, and a Fab sequence is amplified by using a specific primer; according to the invention, a rabbit Fc structural domain is used as an antigen, a Fab antibody capable of being combined with CD30 protein is obtained by screening through a yeast display technology, a Fab sequence is combined with the rabbit Fc structural domain to obtain high-purity fusion protein, and the fact that the Fab antibody has relatively strong activity with CD30 and has specific binding capacity with tumor cells is verified at the cellular level.

The present invention provides novel bispecific antibodies that bind to human CD30 and uses thereof. Methods of treating cancer using the bispecific antibodies described herein are also provided.

The present invention provides a non-human animal expressing human or chimeric (e.g., humanized) CD30L and / or CD30 proteins and methods of use thereof.

The invention relates to a gene-edited cytotoxic cell comprising a chimeric antigen receptor (CAR) that binds CD30, for use in the treatment of an infection, in which infected cells express CD30. In embodiments, the treatment comprises the cytotoxic cell binding to a human target cell, which is infected with a chronic inflammatory virus and expresses CD30. In embodiments, the treatment comprises cytotoxic activity against a reservoir of infected human CD30-expressing target cells in a subject with a chronic viral infection with associated pathologies, immune dysregulations and autoimmune diseases. Corresponding medical uses and methods of treatment are encompassed by the present invention. In another aspect, the invention relates to the CD30-CAR-expressing gene-edited cytotoxic cell as described herein. In other aspects, the invention relates to the CD30-CAR nucleic acid construct and the CAR polypeptide as described herein.

The present disclosure relates to expanding and production of gamma delta (γδ) T cells, e.g., Vδ1+ γδ T cells. In particular, the present disclosure provides improved methods and processes for activating and expanding γδ T cells (e.g., Vδ1+ γδ T cells) using combined CD3 and CD30 agonists and cytokines.

The method comprises providing a culture of human pluripotent stem cells affixed to a first matrix comprising a first laminin; exposing the stem cells to a differential medium for a first period of time from 15 days to 50 days to obtain a first adherent cell population comprising RPE cells and / or ancestors thereof; dissociating the first population from the first matrix at the end of the first time period; re-planking the dissociated first cell population on a second substrate comprising a second laminin; and culturing the re-planked first cell population on a second substrate for a second period of time to obtain an expanded and mature second cell population comprising RPE cells. The first and second laminins may be independently selected from the group consisting of LN-521, LN-511, LN-111, and LN-121, and are intact proteins or protein fragments. In some embodiments, the cell surface marker, which can be used to generate RPE cells in vitro, is selected from the group consisting of CD140b, CD56, CD104, CD164, CD220, EGFR, GD2, CD184, CD10, CD30, CD49a, CD49b, CD50, CD171, TRA-1-60, and CD326, preferably CD140b, CD56, GD2, and / or CD184. Also included are RPE cells so produced, as well as materials and compositions that utilize such RPE cells for various treatments.

To provide methods of treating a disorder characterized by pathological activity of CD30+ cells, such as in certain solid, hematological and lymphoid cancers, in a non-adult human subject by administering an effective amount of an anti-CD30 ADC (antibody drug conjugate), such as, Brentuximab Vedotin, to the subject.SOLUTION: The invention is based, at least in part, on applicant's discovery that a body surface area (BSA)-adjusted dose of an anti-CD30 ADC provides a more consistent exposure to the ADC across non-adult human subjects compared to weight-adjusted doses of an anti-CD30 ADC, as assessed by area under the curve (AUC).SELECTED DRAWING: None

The invention discloses a multiplex fluorescence immunohistochemical detection kit for rare lymphoma and application of the multiplex fluorescence immunohistochemical detection kit. The multiplex fluorescence immunohistochemical detection kit for rare lymphoma comprises a primary antibody reagent and a fluorescence staining reagent, the primary antibody reagent is prepared from a rabbit anti-human CD15 monoclonal antibody, a rabbit anti-human CD30 monoclonal antibody, a KI-67 monoclonal antibody, a rabbit anti-human CD79b monoclonal antibody, a rabbit anti-human CD3 monoclonal antibody and a rabbit anti-human CD20 monoclonal antibody. When the multiplex fluorescence immunohistochemical detection kit for the rare lymphoma is used, a false positive result caused by channel spectrum crosstalk is avoided to the greatest extent through a specific staining sequence of each target protein and fluorescein matching, and the purpose of detecting the rare lymphoma, especially the rare type of lymphoma, is achieved. The kit can be used for synchronous detection of lymphoma, such as hodgkin lymphoma, mantle cell lymphoma and marginal region lymphoma, and provides a reliable basis for lymphoma immune targeted therapy.

A recombinant natural killer (NK)-92 cell transfected with a nucleic acid and gamma (γ) irradiated, wherein the nucleic acid encodes: a homing receptor and / or cytokine; an antigen binding protein or c

Aspects of the present disclosure include improvements in chimeric antigen receptor (CAR) constructs, immune cells comprising CARs, and methods of making and using such constructs and / or cells in the treatment of diseases (e.g., cancer). Disclosed are immune cells comprising CD30-derived hinges and / or transmembrane CARs and methods of using such cells to treat malignancies (e.g., B-cell malignancies). Also disclosed are polynucleotides encoding a CAR comprising a CD30-derived hinge and / or a transmembrane domain, as well as cells comprising such polynucleotides and pharmaceutical compositions comprising such cells.

Provided herein are antibody-drug conjugates that bind to CD30 comprising an anti-CD30 antibody or an antigen-binding fragment thereof and methods of using the same to treat cancer in a subject.

Provided herein are antibody-drug conjugates that bind to CD30 comprising an anti-CD30 antibody or an antigen-binding fragment thereof and methods of using the same to treat cancer in a subject.

The present application relates to a kind of chimeric antigen receptors comprising costimulatory receptors, the structure of the chimeric antigen receptor is scFv (X)-(Y) CD3 zeta-2A-(Z);Wherein, X includes tumor targeting antibody or can be combined with tumor specific ligand, receptor;Y is the intracellular region of costimulatory receptor, Z is costimulatory receptor, the costimulatory receptor is selected from ICOS, CD28, CD27, HVEM, LIGHT, CD40L, 4-1BB, OX40, DR3, GITR, CD30, TIM1, SLAM, CD2, CD226.The present application also provides a kind of CAR-T cell constructed by the recombinant expression vector of the above-mentioned chimeric antigen receptor and its preparation method and application.The CAR-T cell described in the present application significantly improves the tumor killing ability and expansion capacity.

The invention relates to a humanized CD30 antibody, a CD30 CAR-T cell and application of the humanized CD30 antibody and the CD30 CAR-T cell. Specifically, the present invention provides a humanized antibody targeting CD30, a chimeric antigen receptor (CAR) fusion protein comprising a humanized antigen binding domain targeting CD30, and an engineered immune cell (e.g., a CAR-T cell) expressing the CAR fusion protein. The CAR-T cell disclosed by the invention has relatively high affinity and biological activity, relatively good amplification performance and relatively good in-vitro and in-vivo anti-tumor effects.

The invention relates to an anti-CD30 nano antibody as well as a preparation method and application thereof. The anti-CD30 nano antibody is obtained through a phage display technology. The method disclosed by the invention is simple and quick to operate; and a mammalian cell expression system induces high-efficiency expression of the antibody, and the activity of the antibody is closer to that of a natural antibody. The anti-CD30 nano antibody which is specifically combined with the Human CD30 is obtained through enzyme-linked immuno sorbent assay (ELISA) and FACS detection.

This invention provides a method for screening peptides that specifically target T cells, comprising providing T cells having a subset selected from CD1, CD2, CD3, CD4, CD5, CD7, CD8, CD16, CD25, CD26, CD27, CD28, CD30, CD38, CD39, CD40L, CD44, CD45, CD62L, CD69, CD73, CD80, CD83, CD86, CD95, CD103, CD119, CD126, CD150, CD152 (CTLA-4), CD153, CD154 (CD40L) The T cells are labeled with at least one of the following surface antigen markers: CD161, CD183, CD223, CD254, CD275, CD45RA, CXCR3, CXCR5, FasL, IL18R1, CTLA-4, OX40, GITR, LAG3, ICOS, PD-1, leu-12, TCR, TLR1, TLR2, TLR3, TLR4, TLR6, NKG2D, CCR, CCR1, CCR2, CCR4, CCR6, and CCR7. The T cells are then contacted with a peptide display library, and target peptides that specifically bind to the T cells are screened therefrom.

The invention provides an anti-PD-1 antibody and an antibody-drug conjugate that binds to CD30 and their use in methods of treating solid tumors. The invention also provides compositions and kits comprising the anti-PD-1 antibody and the antibody-drug conjugate that binds to CD30 for use in treating solid tumors.

A chimeric antigen receptor (CAR) is provided, the CAR comprising a CD30 binding domain comprising a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCDR2), a heavy chain complementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDRl), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3), and a hinge region derived from CD28.

Methods for the treatment of CD30-expressing cancers are provided. The methods comprise administering to a subject in need thereof a weekly dose of from about 0.8 mg / kg to about 1.8 mg / kg of an antibody-drug conjugate compound having formula I.:or a pharmaceutically acceptable salt thereof;wherein:mAb is an anti-CD30 antibody unit,S is a sulfur atom of the antibody,A- is a Stretcher unit, andp is from about 3 to about 5.

Provided is a method for screening polypeptides that specifically target T cells, comprising: providing T cells having a surface antigen marker selected from at least one of CD1, CD2, CD3, CD4, CD5, CD7, CD8, CD16, CD25, CD26, CD27, CD28, CD30, CD38, CD39, CD40L, CD44, CD45, CD62L, CD69, CD73, CD80, CD83, CD86, CD95, CD103, CD119, CD126, CD150, CD152 (CTLA-4), CD153, CD154 (CD40L), CD161, CD183, CD223, CD254, CD275, CD45RA, CXCR3, CXCR5, FasL, IL18R1, CTLA-4, OX40, GITR, LAG3, ICOS, PD-1, leu-12, TCR, TLR1, TLR2, TLR3, TLR4, TLR6, NKG2D, CCR, CCR1, CCR2, CCR4, CCR6, and CCR7; and contacting the T cells with a polypeptide display library, and screening therefrom target polypeptides that specifically bind to the T cells.

Aspects of the present disclosure include improvements to chimeric antigen receptor (CAR) constructs, CAR comprising immune cells, as well as methods for making such constructs and / or cells and methods for their use in treatment of disease (e.g., cancer). Disclosed are immune cells comprising CARs comprising CD30-derived hinge and / or transmembrane and methods for use of such cells in treatment of malignancies (e.g., B-cell malignancies). Also disclosed are polynucleotides encoding a CAR comprising CD30-derived hinge and / or transmembrane domains, as well as cells comprising such polynucleotides and pharmaceutical compositions comprising such cell

The present invention relates to a chimeric antigen receptor including a CD30-derived intracellular signaling domain, immune cells expressing same, and uses thereof. More specifically, the present invention is designed to use a chimeric antigen receptor including a portion of the sequence of TRAF-binding domain within the CD30 domain as an intracellular signaling domain to increase the proliferation and survival of immune effector cells, thereby providing an effect of enhancing antitumor efficacy and cytokine secretion.