34 results about "Programmed cell death 1" patented technology

An anti-CTLA4 (cytotoxic T lymphocyte associated antigen 4) and anti-PD-1 (programmed cell death 1) bifunctional antibody. a pharmaceutical composition thereof and use thereof. Particularly, the anti-CLTA4 and anti-PD-1 bifunctional antibody comprises a first protein functional domain that targets PD-1 and a second protein functional domain that targets CTLA-4. The bifunctional antibody can bind to CTLA-4 and PD-1 specifically, relieve immunosuppression of CTLA4 and PD-1 on an organism specifically, activate T lymphocytes, and thus has good application prospects.

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 present disclosure generally relates to binding agents capable of targeting tumor cells and / or immune cells and their use to treat cancer. The binding agents of the present disclosure comprise one or more antigen-binding domains of a single-domain antibody capable of binding to cluster of differentiation 36 (CD36), programmed cell death protein 1 (PD-1), and / or cluster of differentiation 47 (CD47). The binding agents of the present disclosure may be monospecific or multispecific and may be in monomeric or multimeric form.

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.

Provided is the use of a genetically engineered phage expressing a first peptide targeting a Programmed Cell Death protein 1 (PD-1) or Programmed Cell Death-Ligand 1 (PD-L1) and a second peptide targeting a cancer-related antigen for enhanced efficacy in cancer treatment. Thus, provided are methods for improved anti-cancer therapy, especially in the treatment of solid tumors, by using a recombinant phage that is capable of specifically targeting the PD-1 / PD-L1 pathway and specifically targeting a cancer antigen, as well as compositions and kits useful for such treatment methods.

To provide engineered PD-1 antibodies and uses thereof.SOLUTION: In some aspects, provided herein are antibodies that bind to PD-1. Antibodies provided herein, in some cases, agonize PD-1 signaling. Antibodies provided herein, in some cases, have modified Fc region. In other aspects, provided herein are compositions, methods of use, methods of making, and kits relating to antibodies that bind to PD-1. In some aspects, provided herein are methods of suppressing immune cells expressing programmed cell death 1 (PD-1), the methods comprising contacting the immune cells with an antibody that specifically binds to PD-1 and enhances an interaction between PD-1 and PD-L1 on a surface of the immune cells.SELECTED DRAWING: None

This disclosure describes an artificial expression construct containing a PD1:cytokine chimeric transgene under the control of an inducible promoter. The artificial expression construct of this disclosure can be used to enhance the function of immune cells (e.g., CAR-T cells) that have recombinant receptors. The inducible PD1:cytokine chimeric transgene disclosed herein enhances the potency of immune cells (e.g., CAR-T cells) that have recombinant receptors, thereby enhancing killing, proliferation of immune cells, and / or cytokine production.

The present invention relates to novel anti-PD-1 (Planned Cell Death 1) antibodies and antigen binding fragments thereof for use in therapeutic and diagnostic methods, and compositions using the same.

Targeting immune checkpoints, such as Programmed cell Death 1 (PD1), has improved survival in cancer patients by unleashing exhausted CD8+ T-cell thereby restoring anti-tumor immune responses. Most patients, however, relapse or are refractory to immune checkpoint blocking therapies. Here, the inventors show that NRP1 is recruited in the cytolytic synapse of PD1+CD8+ T-cells, interacts and enhances PD-1 activity. In mice, CD8+ T-cell specific deletion of Nrp1 improves spontaneous and anti PD1 antibody anti-tumor immune responses. Likewise, in human metastatic melanoma, the expression of NRP1 in tumor infiltrating CD8+ T-cells predicts poor outcome of patients treated with anti-PD1 (e.g. pembrolizumab). Finally, the combination of anti-NRP1 and anti-PD1 antibodies is synergistic in human, specifically in CD8+ T-cells anti-tumor response. Thus the therapeutic inhibition of NRP1 alone or combined with an immune checkpoint inhibitor (e.g. anti-PD1 antibody) could efficiently repress tumor growth in human cancer. The present invention also relates to multispecific antibodies comprising at least one binding site that specifically binds to an immune checkpoint molecule (e.g. PD-1), and at least one binding site that specifically binds to NRP-1. The present invention also relates to a population of cells engineered to express a chimeric antigen receptor (CAR) and wherein the expression of NRP-1 in said cells is repressed.

The present invention provides a means or the like capable of temporarily inhibiting expression of PD-1 or CTLA-4 protein. The present invention relates to an antisense oligonucleotide or the like capable of hybridizing with a nucleic acid sequence of an mRNA precursor and / or mature mRNA of Programmed Cell Death 1 (PD-1) protein or Cytotoxic T-lymphocyte Antigen-4 (CTLA-4) protein and suppressing or inhibiting the expression of PD-1 protein or CTLA-4 protein.

The present invention relates to 1,2,4-oxadiazole and thiadiazole compounds of formula (I). The present invention also relates to the use of the compounds of formula (I) to inhibit the programmed cell death 1 (PD1) signaling pathway and / or for treatment of disorders by inhibiting an immunosuppressive signal induced by PD-1, PD-L1 or PD-L2.

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 relates to genetically modified T cells or chimeric antigen receptor (CAR) T cells, comprising genetic modifications that inhibit or inactivate the expression of prolyl 4 hydroxylase subunit alpha 1 (P4HA1) and / or programmed cell death 1 (PD1) in the T cells or CAR T cells. The present disclosure also relates to methods of treating cancer comprising administration of the modified T cells or CAR T cells as disclosed herein; or administration of P4HA1 inhibitors and / or PD1 / PD-1L inhibitors.

Disclosed herein is a composition including a recombinant nucleic acid sequence that encodes an antibody or fragment thereof that targets programmed cell death protein 1 (PD-1). The disclosure also provides a method of preventing and / or treating disease, such as cancer, in a subject using the composition of the invention.

Described herein are bicyclic peptides which are high affinity binders of programmed cell death 1 ligand 1 (PD-L1). Also provided are drug conjugates comprising the peptides described herein conjugated to one or more effector and / or functional groups. Also provided are pharmaceutical compositions comprising the peptides and drug conjugates described herein, and methods of using the peptide ligands and drug conjugates described herein for treating diseases mediated by PD-L1.

The present invention relates to new anti-PD-1 (Programmed cell death 1) antibodies and antigen-binding fragments thereof for therapeutic and diagnostic methods and compositions using them.

Method and compositions for treating glioblastoma (GBM) and other cancers is disclosed, involving the combination of radiation therapy (RT), fatty acid synthase (FASN) inhibitors, and programmed cell death protein 1 (PD-1) inhibitors or programmed death ligand 1 (PD-L1) inhibitors. The disclosed approach addresses the technical problem of RT-induced immunosuppression and resistance in cancers by targeting RT-induced lipid metabolism, which promotes immune escape. FASN inhibitors block fatty acid synthesis, enhancing immune cell infiltration and restoring anti-tumor immunity. PD-1 / PD-L1 inhibitors further counteract immunosuppressive pathways to improve therapeutic efficacy. This combination therapy prolongs survival, induces immune memory, and is applicable to other cancers, including those exhibiting increased lipid content post-RT or chemotherapy, including melanoma, breast cancer, and lung cancer.

The disclosure provide means and methods for interfering with Programmed Cell Death 1 protein (PD-1) and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) mediated inhibition in a PD-1 and / or TIM-3 positive cell. A method may comprise contacting said cell with an antibody or a functional part, derivative and / or analogue thereof that comprises a variable domain that can bind to an extracellular part of PD-1 and a variable domain that can bind to an extracellular part of TIM-3, thereby inhibiting PD-1 and / or TIM-3 mediated activity in said cell. The invention also provides antibodies or variant thereof that comprises a variable domain that can bind to an extracellular part of PD-1 and a variable domain that can bind to an extracellular part of TIM-3.

Provided herein are antibody molecules that specifically bind to Programmed Cell Death Protein 1 (PD1) and Vascular Endothelial Growth Factor Receptor 2 (VEGFR2), related nucleic acid molecules, vectors, and host cells. Also provided herein are medical uses of such antibody molecules.

The present disclosure provides a method for treating, reducing the severity of, or inhibiting the growth of MUC16-expressing cancer (e.g., ovarian cancer or endometrial cancer). In certain embodiments, the method of the present disclosure comprises the step of administering a therapeutically effective amount of an antibody or antigen-binding fragment thereof that specifically binds to a programmed cell death 1 (PD-1) receptor, or a bispecific antibody or antigen-binding fragment thereof that specifically binds to mucin 16 (MUC16) and CD28 in combination with a bispecific antibody or antigen-binding fragment thereof that specifically binds to MUC16 and CD3, to a subject in need thereof.

The present disclosure relates to antibodies and anti-gen-binding fragments that bind specifically to the human programmed cell death protein 1 (PD-1) and methods for treating cancer or other diseases with said antibodies and antigen-binding fragments.

Provided are novel monoclonal antibodies or antibody fragments against protein programmed cell death 1 (PD-1). The antibodies or antibody fragments disclosed can block the binding of the PD- L1 ligand to PD-1 and provide potent agents for the treatment of cancers via the modulation of human immune function. Also provided are novel multispecific antibodies directed against PD-1 and cytotoxic T-lymphocyte-associated protein 4 CTLA-4.

Methods of treating patients having HER2-positive cancer are provided. Certain methods involve treatment of HER2 positive breast cancer using a programmed cell death protein 1 (PD-1) binding antagonist or a programmed death ligand 1 (PD-L1) binding antagonist in combination with trastuzumab and pertuzumab or with trastuzumab emtansine. The treatment regimen may be used in various clinical settings, for example, for treatment in the neoadjuvant or metastatic setting.

Provided herein are antibody molecules that bind specifically to Programmed cell death 1 (PD1) and Vascular endothelial growth factor receptor 2 (VEGFR2), related nucleic acid molecules, vectors and host cells. Also provided herein are medical uses of such antibody molecules.

Provided are novel monoclonal antibodies or antibody fragments against protein programmed cell death 1 (PD-1). The antibodies or antibody fragments disclosed can block the binding of the PD- L1 ligand to PD-1 and provide potent agents for the treatment of cancers via the modulation of human immune function. Also provided are novel multispecific antibodies directed against PD-1 and cytotoxic T-lymphocyte-associated protein 4 CTLA-4.

Provided is a pharmaceutical combination, comprising (E)-N-hydroxy-3-(l-(phenylsulfonyl)- indolin-5-yl)-acrylamide, a vascular endothelial growth factor (VEGF) inhibitor, and a programmed cell death protein 1 (PD-l) / programmed cell death ligand 1 (PD-L1) pathway inhibitor. Also provided is a method for treating cancer using the pharmaceutical combination. The pharmaceutical combination has been demonstrated to synergistically enhance tumor growth inhibition, improve objective response rates (ORR), and achieve long-term survival rates in cancers refractory to existing therapies, including microsatellite-stable (MSS) colorectal cancer and hepatocellular carcinoma.

Provided are compositions and methods that relate to therapy of B cell diseases and include discovery of novel molecular heterogeneity of the signaling component (i.e., CD79) of human B cell antigen receptor (BCR). The method includes co-administering antibodies or antigen binding fragments thereof that specifically bind CD79a and CD79b to provide synergistic therapy of B cell tumors. The method may further include administering an antibody that specifically binds to an immune checkpoint molecule, such as programmed cell death protein 1 (PD-1).

Provided herein are methods for preventing an mpox virus infection, reducing the effects of an mpox virus infection, or inducing a protective immune response against an mpox virus in a subject, such as a human, comprising administering to the subject a pharmaceutical composition comprising a modified vaccinia Ankara viral vector encoding programmed cell death protein 1 (PD-1) inhibitory peptide LD10 (MVA-LD10).

The present application describes isolated polypeptides that are mutants of Programmed Cell Death 1 Ligand 2 ("PD-L2") and are capable of activating or inhibiting immune cells by activating or inhibiting Programmed Cell Death Protein 1 ("PD-1"). The present application further describes pharmaceutical compositions comprising the polypeptides and methods of using the polypeptides.