104 results about "CD30" patented technology

The present invention relates to methods and compositions for the treatment of Hodgkin's Disease, comprising administering proteins characterized by their ability to bind to CD30, or compete with monoclonal antibodies AC10 or HeFi-1 for binding to CD30, and exert a cytostatic or cytotoxic effect on Hodgkin's disease cells in the absence of effector cells or complement. Such proteins include derivatives of monoclonal antibodies AC10 and HeFi-1. The proteins of the invention can be human, humanized, or chimeric antibodies; further, they can be conjugated to cytotoxic agents such as chemotherapeutic drugs. The invention further relates to nucleic acids encoding the proteins of the invention. The invention yet further relates to a method for identifying an anti-CD30 antibody useful for the treatment or prevention of Hodgkin's Disease.

An antibody that targets CD30, wherein the antibody comprises at least one modification relative to a parent antibody and the antibody binds with altered affinity to an FcγR or alters effector function as compared to the parent antibody. Also disclosed are methods of using the anti-CD30 antibody.

CD30 is a receptor expressed on cells of Hodgkin's disease and certain leukemias. The extracellular portion of CD30 is cleaved, releasing a form known as sCD30. The invention relates in part to the discovery that a residual, extracellular “stalk” of CD30 remains after cleavage of sCD30. The stalk provides an advantageous and previously unrecognized target for immunotoxins. The invention provides antibodies that bind to the CD30 stalk or to epitopes destroyed upon the cleavage of CD30 which results in the stalk. The invention further provides new anti-CD30 antibodies that form effective immunotoxins and are particularly suitable for making disulfide stabilized Fv (“dsFv”)-immunoconjugates. The dsFv immunoconjugates can be used as reagents to label CD30-expressing cancer cells or to inhibit the growth of CD30-expressing cancer cells. Moreover, the invention provides anti-CD30 antibodies that activate complement-dependent cytotoxicity.

The invention pertains to anti-CD30 antibodies that lack fucosyl and xylosyl residues. The antibodies of the invention exhibit increased antibody-dependent cellular cytotoxicity (ADCC) activity, including the ability to lyse CD30-expressing cell lines that are not lysed by the fucosylated and xylosylated form of the antibodies. The invention also provides host cells that express the anti-CD30 antibodies that lack fucosyl and xylosyl residues, wherein the host cells are deficient for a fucosyltransferase and a xylosyltransferase. Methods of using the antibodies to inhibit the grown of CD30+ cells, such as tumor cells, are also provided.

The present invention relates to methods and compositions for the treatment of Hodgkin's Disease, comprising administering proteins characterized by their ability to bind to CD30, or compete with monoclonal antibodies AC10 or HeFi-1 for binding to CD30, and exert a cytostatic or cytotoxic effect on Hodgkin's disease cells in the absence of effector cells or complement. Such proteins include derivatives of monoclonal antibodies AC10 and HeFi-1. The proteins of the invention can be human, humanized, or chimeric antibodies; further, they can be conjugated to cytotoxic agents such as chemotherapeutic drugs. The invention further relates to nucleic acids encoding the proteins of the invention. The invention yet further relates to a method for identifying an anti-CD30 antibody useful for the treatment or prevention of Hodgkin's Disease.

The invention discloses a transgenic T cell of a targeted CD30 antigen. The transgenic T cell is a primary cell which is integrated with a gene shown as SEQ ID NO:2 and encoding the targeted CD30 antigen, and knocks out a PD1 gene and / or CTLA4 gene, or is a primary cell containing a recombinant lentivirus expression vector (including a gene which is shown as SEQ ID NO:2 and encodes the targeted CD30 antigen and shRNA of a targeted PD1 gene or / and shRNA of a targeted CTLA4 gene); the primary cell is CD4+T cell or CD8+T cell. A preparation method comprises the following steps: firstly, carryingout lentivirus infection on the CD4+T cell or the CD8+T cell; secondly, mixing gRNA, CRISPR-cas9mRNA and HDR, and carrying out electroporation recombination on the T cell to obtain a finished product.According to the transgenic T cell disclosed by the invention, a recognition sequence of an EGFR (Epidermal Growth Factor Receptor) is introduced in carT construction; if necessary, a carT cell can be eliminated by using EGFR monoclonal antibody Cetuximab, the PD1 gene and the CTLA4 gene are knocked out or silenced, inhibition of the gene to the carT cell is eliminated, and the function of overcoming a tumor microenvironment and inhibiting immune cells by the carT cell are enhanced.

The invention provides a method of modulating a T cell immune response by modulating DR3 function in the T cell, wherein the T cell response causes a symptom of inflammatory lung disease. The invention also provides a method of treating a reactive airway disease in an animal subject by administering to the subject an agent which modulates at least one functional activity of CD30. The invention additionally provides a method for treating an inflammatory lung disease by administering an agent that decreases the activity of DR3 or CD30, whereby IL-13 expression is decreased.

The invention provides a duplex-specific chimeric antigen receptor. The duplex-specific chimeric antigen receptor is composed of a signal peptide, two specific antigen binding fragments, an extra-membrane spacer region, a transmembrane region and an intracellular costimulatory signal region, wherein a first antigen which is recognized and bound by the specific antigen binding fragments is one of CD19, CD20, CD22, CD33, CD269, CD138, CD79a, CD79b, CD23, ROR1, CD30, a B cell surface antibody light chain, CD44, CD123, LewisY, CD7 or CD46; a second antigen which is recognized and bound by the specific antigen binding fragments is CD38; the two specific antigen binding fragments are connected through one connection peptide; the duplex-specific chimeric antigen receptor can be used for respectively recognizing two tumor-related antigens through constructing a low-affinity chimeric antigen receptor and a high-affinity chimeric antigen receptor and has very strong specificity. Furthermore, theinvention further provides application of the duplex-specific chimeric antigen receptor to tumor therapy.

The invention discloses a lymphoblastic leukemia CAR-T (Chimeric Antigen Receptor-T Cell Immunotherapy) therapy carrier based on an OCTS (One CAR with Two SeFvs) technology. The lymphoblastic leukemia CAR-T therapy carrier comprises a lentivirus skeleton plasma, a human EF1alpha promoter, an OCTS chimeric receptor structural domain and an IL6R single-chain antibody, wherein the OCTS chimeric receptor structural domain comprises a CD8 leader chimeric receptor signal peptide and two groups of single-chain antibodies; the first group of single-chain antibodies is selected from any one of the following four groups of single-chain antibodies: a CD20 single-chain antibody light chain VL and a CD20 single-chain antibody heavy chain VH, a CD22 single-chain antibody light chain VL and a CD22 single-chain antibody heavy chain VH, a CD30 single-chain antibody light chain VL and a CD30 single-chain antibody heavy chain VH, and a CD123 single-chain antibody light chain VL and a CD123 single-chain antibody heavy chain VH; and the second group of the single-chain antibodies is a CD19 single-chain antibody light chain VL and a CD19 single-chain antibody heavy chain VH, an antibody Inner-Linker, a single-chain antibody Inter-Linker, a CD8-Hinge chimeric receptor linker, a CD8 Transmembrane chimeric receptor transmembrane zone, a TCR (T Cell Receptor) chimeric receptor T cell activation domain and a chimeric receptor co-stimulator zone. Besides, the invention discloses a constructing method for the carrier and application of the carrier to preparation of a drug for treating lymphoblastic leukemia.

A method of analyzing a biological sample suspected of having classic Hodgkin lymphoma, comprising (1) detecting, in a single sample, for the expression of at least two biomarkers selected from CD30, CD15, CD20, CD45, CD3, Pax-5, CD79A, BOB1 and OCT-2; and (b) analyzing the sample based on the presence, absence and / or expression level of the at least two biomarkers. Also provided is a method wherein all the nine biomarkers are analyzed on a single sample. Further provided are method for diagnosing classical Hodgkin lymphoma, as well as system and kit that comprise the means for executing the novel methods.

Isolated human monoclonal antibodies which bind to CD30 (e.g., human CD30) are disclosed. The human antibodies can be produced in a non-human transgenic animal, e.g., a transgenic mouse, capable of producing multiple isotypes of human monoclonal antibodies by undergoing V-D-J recombination and isotype switching. Also disclosed are derivatives of the human antibodies (e.g., bispecific antibodies and immunoconjugates), pharmaceutical compositions comprising the human antibodies, non-human transgenic animals and hybridomas which produce the human antibodies, and therapeutic and diagnostic methods for using the human antibodies.

The invention relates to a chimeric antigen receptor (CAR) containing a third signal receptor. The structure of the CAR is scFv(X)-(Y)CD3zeta-MN, wherein X comprises a tumor-targeting antibody or a ligand and receptor capable of being specifically combined with tumors, Y is an intracellular region of a costimulatory receptor, the costimulatory receptor is selected from ICOS, CD28, CD27, HVEM, LIGHT, CD40L, 4-1BB, OX40, DR3, GITR, CD30, TIM1, SLAM, CD2 and CD226, M is an intracellular region of a cytokine receptor of a gamma chain family, the cytokine receptor is selected from IL2Ra, IL2Rb, IL4Ra, IL7Ra, IL9Ra, IL15Ra and IL21Ra, and N is an IL2Rg intracellular region. The invention further relates to a CAR-T cell constructed from a recombinant expression vector of the CAR and a preparationmethod and application of the CAR-T cell. Through the CAR-T cell, the tumor killing ability and the amplification ability are significantly improved, the CAR-T cell contains the third signal receptor, the third signal receptor has the potential function of effect enhancement and only has the effect on the CAR-T cell, and the risk of causing immune side effects is reduced.

The invention pertains to anti-CD30 antibodies that lack fucosyl and xylosyl residues. The antibodies of the invention exhibit increased antibody-dependent cellular cytotoxicity (ADCC) activity, including the ability to lyse CD30-expressing cell lines that are not lysed by the fucosylated and xylosylated form of the antibodies. The invention also provides host cells that express the anti-CD30 antibodies that lack fucosyl and xylosyl residues, wherein the host cells are deficient for a fucosyltransferase and a xylosyltransferase. Methods of using the antibodies to inhibit the growth of CD30 cells, such as tumor cells, are also provided.

In a first aspect, the present disclosure relates to genetically modified T-cells having a chimeric antigen receptor for use in adoptive cell therapy for treating CD30+cancer in a subject need thereof. In particular, the present disclosure relates to a T-cell containing a specific chimeric antigen receptor being toxic to CD30+cancer cells while being non-toxic to CD30+non-cancer cells. In a further aspect, the present disclosure relates to a specific chimeric antigen receptor and the nucleic acid molecule encoding the receptor as well vectors and cells containing the same. Finally, the present disclosure relates to the use of the chimeric antigen receptor for use in improving persistence and amplification of lymphocyte containing the same and the use of specific peptides for improving persistence and amplification of genetically modified lymphocytes expressing the same.

An antibody that targets CD30, wherein the antibody comprises at least one modification relative to a parent antibody and the antibody binds with altered affinity to an FcgR or alters effector function as compared to the parent antibody. Also disclosed are methods of using the anti-CD30 antibody.

CD30 is a receptor expressed on cells of Hodgkin's disease and certain leukemias. The extracellular portion of CD30 is cleaved, releasing a form known as sCD30. The invention relates in part to the discovery that a residual, extracellular “stalk” of CD30 remains after cleavage of sCD30. The stalk provides an advantageous and previously unrecognized target for immunotoxins. The invention provides antibodies that bind to the CD30 stalk or to epitopes destroyed upon the cleavage of CD30 which results in the stalk. The invention further provides new anti-CD30 antibodies that form effective immunotoxins and are particularly suitable for making disulfide stabilized Fv (“dsFv”)-immunoconjugates. The dsFv immunoconjugates can be used as reagents to label CD30-expressing cancer cells or to inhibit the growth of CD30-expressing cancer cells. Moreover, the invention provides anti-CD30 antibodies that activate complement-dependent cytotoxicity.

Chimeric antigen receptors (CARs) that specifically bind to and immunologically recognize CD30 are disclosed. Related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions relating to the CARs are also disclosed. Methods of treating or preventing a condition in a mammal, wherein the condition is cancer, are also disclosed.