209 results about "Programmed death" patented technology

This disclosure provides a method for treating a subject afflicted with a lung cancer, which method comprises administering to the subject therapeutically effective amounts of: (a) an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity; and (b) an antibody or an antigen-binding portion thereof that specifically binds to a Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) and inhibits CTLA-4 activity.

The disclosure provides a method of treating a human subject afflicted with lung cancer (e.g., non-small cell lung cancer (NSCLC)) with a programmed death-1 (PD-1) pathway inhibitor (e.g., an anti-PD-1 antibody) and a concurrent chemoradiotherapy (CCRT, e.g., a platinum doublet chemotherapy (PDCT) and a radiation therapy) followed by a combination of a PD-1 pathway inhibitor (e.g., an anti-PD-1 antibody) and a lymphocyte activation gene-3 (LAG-3) antagonist (e.g., an anti-LAG-3 antibody). In some aspects, the method comprises a recovery period that begins upon completion of the treatment with the PD-1 pathway inhibitor and the CCRT and ends at the start of the treatment with the combination of the PD-1 pathway inhibitor and the LAG-3 antagonist.

The invention discloses application of an MCU (microprogrammed control unit) inhibitor in preparation of a medicine for preventing or treating intestinal ischemia-reperfusion injury, and relates to the technical field of biological medicine, and the MCU inhibitor comprises one or two of a reagent for inhibiting MCU gene expression and a reagent for inhibiting MCU protein activity. The MCU inhibitor disclosed by the invention is beneficial to relieving intestinal mucosa injury and inflammatory change of intestinal tissues, improving completeness of a villus structure, reducing pathological injury degree score of the intestinal tissues and relieving cell apoptosis degree in the intestinal tissues, so that the MCU inhibitor is beneficial to relieving programmed death of intestinal mucosa cells; as a main component, the pharmaceutical composition is beneficial for preventing or treating intestinal ischemia-reperfusion injury.

This disclosure provides novel bispecific antibodies that specifically bind to CD47 and Programmed Death-Ligand 1 (PD-L1). The disclosure further relates to methods of making the bispecific antibodies and nucleic acids encoding the antibodies. The disclosure further relates to therapeutic methods for use of the bispecific antibodies in the treatment of a condition associated with malignant cells expressing CD47 and / or PD-L1.

The invention discloses a PD-1 (programmed death-1) monoclonal antibody and application thereof, the invention provides the monoclonal antibody, an antibody heavy chain complementarity determining region comprises CDR-H1, CDR-H2 and CDR-H3 which are respectively shown as SEQ ID NO.1-3, and an antibody light chain complementarity determining region comprises CDR-L1, CDR-L2 and CDR-L3 which are respectively shown as SEQ ID NO.4, LAS (LAS) and SEQ ID NO.5.

The present disclosure provides recombinantly manufactured fusion proteins comprising a Programmed Death-Ligand 1 (PD-L1) protein fragment or an analog thereof linked to a canine Fc fragment. Embodiments include the administration of the fusion proteins to patients as a treatment for cancers, tumors or other diseases associated with expression of the PD-L1 protein in dogs. Exemplary Fc fusion proteins and pharmaceutical formulations of exemplary Fc fusion proteins are provided, in addition to methods of use and preparation.

The present disclosure relates to 3-substituted 1,2,4-oxadiazole compounds and their derivatives, which are useful as V-domain immunoglobulin suppressor of T-cell activation (VISTA) inhibitors or as dual inhibitors of VISTA and the programmed cell death 1 (PD-1) signaling pathway. The disclosure also relates to treatment of disorders by inhibiting an immunosuppressive signal induced by VISTA and its ligands, PD-1, PD-L1, and / or PD-L2.

The present invention relates to a composition comprising a combination of an anti-PD-1 antibody and an additional antibody. Pharmaceutical compositions are provided, which comprise a combination of anticancer agents that are a first antibody and a second antibody. In some embodiments, the first antibody is an anti-programmed death-1 (PD-1) antibody. In certain embodiments, the composition is a fixed-dose formulation. In certain embodiments, the composition is administered in an absolute dose. The present disclosure also provides a kit for treating a subject having a disease, the kit comprising a dose of any of the compositions disclosed herein and instructions for using the composition to treat a disease in any of the disclosed methods.

The present disclosure provides bispecific antibodies useful in gene therapy. Specifically, the invention provides a bispecific antibody, and the bispecific antibody comprises a heavy chain variable region (VHVEGF) and a light chain variable region (VLVEGF) which are targeted to a vascular endothelial growth factor (VEGF), and a heavy chain variable region (VHPD-L1) and a light chain variable region (VLPD-L1) which are targeted to a programmed death receptor-ligand 1 (PD-L1). The bispecific antibody provided by the disclosure can be used for gene therapy, such as AAV or mRNA mediated gene therapy, and can effectively block PD-1 / PD-L1 and VEGF / VEGFR pathways, and inhibit tumors in vitro and in vivo.

The present application provides antibodies including antigen binding fragment thereof that specifically recognizing programmed cell death 1 ligand 1 (PD-L1). Also provided are methods of making and using these antibodies.

The invention discloses an anti-tumor pharmaceutical composition based on NBDHEX and application of the anti-tumor pharmaceutical composition in treatment of immunosuppressive malignant tumors. The pharmaceutical composition comprises NBDHEX (6-(7-nitro-2, 1, 3-benzoxadiazol-4-ylthio) hexanol) and a PD-1 (programmed death-1) inhibitor, and is characterized in that the NBDHEX (6-(7-nitro-2, 1, 3-benzoxadiazol-4-ylthio) hexanol) and the PD-1 inhibitor are used as raw materials. The NBDHEX can induce tumor cells to generate immunogenic death and promote tumor antigen release, DAMPs signal activation and dendritic cell maturation, so that an immunosuppressive tumor microenvironment is remodeled, and CD8 + T cell infiltration and effector functions are enhanced. The pharmaceutical composition can significantly improve the anti-tumor immune response intensity and the treatment response rate. Animal experiments and cell experiments verify the synergistic anti-tumor effect of the composition in a lymphoma model. The immunosuppressive malignant tumors are suitable for treatment of various immunosuppressive malignant tumors including lymphoma, and are especially suitable for patients with poor single-drug reaction or drug resistance to immune checkpoint inhibitors, and a new way is provided for clinical treatment of tumors.

This disclosure provides a method for treating a subject afflicted with a renal cancer, which method comprises administering to the subject therapeutically effective amounts of: (a) an anti-cancer agent which is an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity; and (b) another anti-cancer agent. The other anti-cancer agent may be an anti-angiogenic tyrosine kinase inhibitor or an anti-Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) antibody. The disclosure also provides a kit for treating a subject afflicted with a renal cancer, the kit comprising a dosage of an anti-PD-1 antibody, a dosage of another anti-cancer agent which is an anti-angiogenic tyrosine kinase inhibitor or an anti-CTLA-4 antibody, and instructions for using the anti-PD-1 antibody and the other anti-cancer agent in any of the disclosed methods for treating a renal cancer.

Described herein are gene features that provide prognosis, diagnosis, treatment and molecular subtype classification of cancer by genomic and epigenomic profiling, including immune checkpoint regulators such as Programmed Death Ligand 1 (PDL-1). Using the methods and compositions described herein, specific and sensitive detection of biomarkers of interest is provided. Such biomarkers indicate disease pathogenesis, which provides opportunities for selection of treatments, including treatment regimens intended to overcome tolerance mechanisms.

The present disclosure describes combination therapies comprising an antagonist of Programmed Death 1 receptor (PD-1), a Lymphocyte-Activation Gene 3 (LAG3) antagonist, and all-trans retinoic acid or a pharmaceutically acceptable salt thereof and the use of the combination therapies for the treatment of cancer.

The present application relates to the technical field of biotechnology, in particular to a programmed death receptor ligand 2 monoclonal antibody and application thereof. The present application provides a PD-L2 monoclonal antibody, amino acid sequences of three CDR regions of a heavy chain thereof; amino acid sequences of three CDR regions of a light chain thereof; or amino acid sequences obtained by substitution, deletion or addition of one or more amino acids of the amino acid sequences, or amino acid sequences functionally identical or similar to the amino acid sequences; or amino acid sequences having at least 80% homology with the sequences. The present application widens the possibility of antibody therapy for blocking PD1 / PD1 ligand, and compared with existing PD-L2 monoclonal antibodies, the 8E3 antibody has unique amino acid sequences and CDR region sequences, high affinity and high specificity. The 8E3 antibody can be used in ELISA, Western blot and flow cytometry detection, and has wide application.

The present disclosure relates to anti-PDL1 (Programmed Death Ligand 1) antibodies, antigen binding fragments thereof, antibody drug conjugates (ADCs) derived therefrom, and uses thereof.

Provided herein are binding molecules that bind to programmed cell death protein 1 (PD-1). Such binding molecules block the interaction between PD-1 and programmed death-ligand 1 and 2 (PD-L1 and PD-L2). Also provided herein are methods of using such binding molecules for preventing and treating cancer.

The present disclosure provides methods for treating, reducing the severity of, inhibiting the growth of a tumor, or inducing necrosis of a tumor, wherein the method includes selecting a patient with cancer (e.g., liver cancer, lung cancer, or head and neck cancer) in need thereof and administering to the patient a therapeutically effective amount of a programmed death 1 (PD-1) inhibitor (e.g., cemiplimab or abioequivalent thereof) as neoadjuvant therapy followed by surgical resection and optional administration of a programmed death 1 (PD-1) inhibitor (e.g., cemiplimab or a bioequivalent thereof) as post-surgery adjuvant therapy. In certain embodiments, the liver cancer is hepatocellular carcinoma (HCC), the lung cancer is non-small cell lung cancer (NSCLC), or the head and neck cancer is head and neck squamous cell carcinoma (HNSCC).

The present invention discloses an anti-programmed death receptor 1 antibody H1 and its application. The amino acid sequences of the CDR1, CDR2, and CDR3 of the heavy chain of the anti-programmed death receptor 1 antibody H1 include the sequences shown in SEQ ID NO.1, SEQ ID NO.2, and SEQ ID NO.3, respectively. The present invention uses PD-1 protein to immunize alpacas. The anti-programmed death receptor 1 antibody H1 obtained has strong affinity and can block the binding of PD-1 and PD-L1, enhance the function of immune cells, and improve the ability of T cells to eliminate tumors.

The invention relates to the technical field of biological medicines, in particular to a polypeptide targeting B cell lymphoma cells, a targeting effect conjugate and application of the polypeptide and the targeting effect conjugate. Wherein the peptide chain length of the polypeptide targeting the B-cell lymphoma cells is 12 amino acids, and the polypeptide is selectively and specifically combined with the B-cell lymphoma cells. The targeting effect conjugate is formed by connecting polypeptide and pro-apoptotic peptide through a connecting peptide. The pro-apoptotic peptide can induce programmed death of target cells by destroying a mitochondrial membrane structure. The molecular weight of the polypeptide is small, the chemical synthesis process is simple, convenient and efficient, high consistency between different batches of products can be ensured in the synthesis process, and a guarantee is provided for subsequent quality control. The small molecular structure is also convenient for sequence optimization and terminal modification, can create extremely favorable conditions for subsequent structure-function relationship research and pharmaceutical development work, and is helpful for accelerating the research and development process of novel therapeutic drugs.

The present disclosure provides methods for treating or inhibiting the growth of a tumor, including selecting a patient with cancer, wherein the patient is immunosuppressed or immunocompromised, and administering to the patient a therapeutically effective amount of a programmed death 1 (PD-1) inhibitor (e.g., an anti-PD-1 antibody, such as cemiplimab or a bioequivalent thereof). In certain embodiments, the cancer is skin cancer, such as cutaneous squamous cell carcinoma.

The invention provides an application of OGA as an inhibition target in preparation of drugs for treating GBC, and relates to the technical field of biomedicine.According to a specific verification test, it is found that GBC cells transfer OGA to neurons through EVs, so that glycosylation of RIPK1 is inhibited, phosphorylation and activation of RIPK1 are promoted, and finally neuronal necroptosis is induced. RIPK1 is a core factor for regulating and controlling cell survival, inflammatory response and programmed death, and is activated through a compound IIb pathway under the action of exogenous OGA. EV-induced invasion and necroptosis can be remarkably inhibited through neuron OGA knock-down, so that the aim of treating GBC is achieved.

The present invention relates to an anti-programmed death receptor 1 antibody A3 and its use. The anti-programmed death receptor 1 antibody A3 comprises a heavy chain variable region, wherein the heavy chain variable region includes CDR1, CDR2, and CDR3; the amino acid sequence of the CDR1 includes the sequence shown in SEQ ID NO.1; the amino acid sequence of the CDR2 includes the sequence shown in SEQ ID NO.2; and the amino acid sequence of the CDR3 includes the sequence shown in SEQ ID NO.3. The antibody of the present invention has high affinity and strong ability to block the binding of PD-1 and PD-L1, and can be used to prepare immune-enhancing drugs.

The invention provides pharmaceutical compositions of anti-PD-1 antibodies or antigen-binding fragments thereof with less than or equal to about 3.0% oxidation of Met105 in the CDRH3 heavy chain region, and PH20 variants or fragments thereof. The invention also provides pharmaceutical compositions comprising anti-PD-1 antibody main species and acidic species thereof, wherein the amount of acidic species is about 1.0-12.0%, and PH20 variants or fragments thereof.

The disclosure provides a method of treating a human subject afflicted with lung cancer with a lymphocyte activation gene-3 (LAG-3) antagonist. In some aspects, the method comprises combination of the LAG-3 antagonist with an additional therapeutic agent (e.g., a programmed death-1 pathway inhibitor) and / or anti-cancer therapy (e.g., chemotherapy such as a platinum doublet chemotherapy).

The present disclosure provides methods of treating a human subject suffering from lung cancer (e.g., non-small cell lung cancer (NSCLC)) using a programmed death-1 (PD-1) pathway inhibitor (e.g., an anti-PD-1 antibody) and synchronous chemoradiotherapy (CCRT, e.g., platinum-based dual drug chemotherapy (PDCT) and radiotherapy), a combination of a PD-1 pathway inhibitor (e.g., an anti-PD-1 antibody) and a lymphocyte activation gene-3 (LAG-3) antagonist (e.g., an anti-LAG-3 antibody) is then used. In some aspects, the methods include a recovery phase that begins after completion of treatment with a PD-1 pathway inhibitor and CCRT, and ends at the beginning of treatment with a combination of a PD-1 pathway inhibitor and a LAG-3 antagonist.

The present invention relates to a PD-L1 specific chimeric antigen receptor and an immune cell comprising the same. Particularly, the PD-L1 specific chimeric antigen receptor comprises a binding domain that specifically binds to programmed death-ligand 1 (PD-L1), thus having excellent PD-L1 specific targeting efficiency, and exhibits excellent anticancer effects against cancer cells expressing PD-L1, and thus can be effectively used in the prevention or treatment of cancer.

This disclosure provides methods for treating tumors, reducing tumor severity, inhibiting tumor growth, or inducing tumor necrosis, wherein the methods include: selecting a patient with cancer (e.g., liver cancer, lung cancer, or head and neck cancer) in need of treatment and administering neoadjuvant therapy to the patient in a combination of a therapeutically effective amount of a programmed death 1 (PD-1) inhibitor (e.g., cimiprimab or its bioequivalent) and radiation therapy (e.g., SBRT) or an anti-LAG-3 antibody (e.g., fenpromab), followed by surgical resection and optionally administration of a programmed death 1 (PD-1) inhibitor (e.g., cimiprimab or its bioequivalent) as postoperative adjuvant therapy. In some embodiments, the cancer is liver cancer, such as hepatocellular carcinoma (HCC).

The present invention relates to a method for treating tumors or inhibiting tumor proliferation, comprising administering, as a neoadjuvant therapy, a therapeutically effective amount of a programmed death-ligand 1 (PD-L1) inhibitor (for example, an anti-PD-L1 antibody) to a cancer patient in need thereof, followed by surgical resection. In particular, the present invention relates to a method for administering a PD-L1 inhibitor as a neoadjuvant therapy prior to surgery to patients with surgically resectable upper gastrointestinal cancer, for example, localized gastric cancer, esophageal cancer or liver cancer. It has been identified that the administration of a PD-L1 inhibitor, particularly an anti-PD-L1 antibody, exhibits an excellent therapeutic effect as a neoadjuvant therapy for patients with surgically resectable localized gastric cancer, esophageal cancer, and liver cancer.

This disclosure provides a method for treating a subject afflicted with tumor, which method comprises administering to the subject an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity. In some embodiments, the tumor is derived from a non-small cell lung cancer (NSCLC). In some embodiments, the tumor expresses Programmed Death Ligand 1 (PD-L1), Serine / Threonine Kinase 11 (STK11), or both PD-L1 and STK11.