Eureka Therapeutics, Inc.

Memorial Sloan Kettering Cancer Center

Su Yan

Cheng Liu

Hong Liu

Yiyang Xu

Jingyi Xiang

David A Scheinberg

Tao Dao

Zhiyuan Yang

Lucas Horan

Jingwei Lu

Vivien Wai-Fan Chan

Pei Wang

Nai-Kong V Cheung

Wei Chan Tai

Mahiuddin Ahmed

Andres Lopez-Albaitero

Brian Wong

Emma Masteller

Katharine Hsu

Ming Cheng

Hongfen Guo

The present application provides antibody-TCR chimeric constructs comprising an antibody moiety that specifically binds to a target antigen fused to a TCRM capable of recruiting at least one TCR-associated signaling module. Also provided are methods of making and using these constructs.

Antibody/T-cell receptor chimeric constructs and uses thereof

The invention relates to antibodies, and in particular, to antibodies exhibiting specificity for Receptor tyrosine kinase-like Orphan Receptors (ROR), and to uses thereof for example in the treatment of cancer. The invention extends to polynucleotide and polypeptide sequences encoding the antibodies, and therapeutic uses thereof, and to diagnostic kits comprising these molecules. The invention also extends to antibody-drug conjugates and to uses thereof in therapy.

Anti-ROR2 antibodies

The presently disclosed subject matter provides antigen-binding proteins that specifically bind to Preferentially expressed antigen of melanoma (PRAME), including humanized, chimeric and fully human antibodies against PRAME, antibody fragments (e.g., scFv, Fab and F(ab)), chimeric antigen receptors (CARs), fusion proteins, and conjugates thereof. The antigen-binding proteins and antibodies bind to a PRAME peptide/HLA class I molecule complex. Such antibodies, fragments, fusion proteins and conjugates thereof are useful for the treatment of PRAME associated diseases, including for example, breast cancer, ovarian cancer, melanoma, lung cancer, gastrointestinal cancer, brain tumor, head and neck cancer, renal cancer, myeloma, neuroblastoma, mantle cell lymphoma, chronic myelocytic leukemia, multiple myeloma, acute lymphoblastic leukemia (ALL), acute myeloid/myelogenous leukemia (AML), Non-Hodgkin lymphoma (NHL), and Chronic lymphocytic leukemia (CLL). The antibodies or antigen binding proteins may comprise one or more framework region amino acid substitutions designed to improve protein stability, antibody binding and/or expression levels.

T cell receptor-like antibodies specific for a PRAME peptide

Described herein are antibodies, fragments thereof and multi-specific binding agents that bind an Epstein-Barr virus (EBV) latent membrane protein 2 (LMP2) peptide presented by HLA class I molecules, in particular, HLA-A02. Also provided herein are methods of using the same or compositions thereof for the detection, prevention and/or therapeutic treatment of diseases characterized by expression of an EBV-LMP2 peptide presented by HLA-A02, in particular, Burkit's lymphoma, Hodgkin's lymphoma and nasopharyngeal carcinoma.

T cell receptor-like antibody agents specific for EBV latent membrane protein 2A peptide presented by human HLA

The invention relates to antibodies, and in particular, to antibodies exhibiting specificity for Receptor tyrosine kinase-like Orphan Receptors (ROR), and to uses thereof, for example in the treatment of cancer. The invention extends to polynucleotide and polypeptide sequences encoding the antibodies, and therapeutic uses thereof, and to diagnostic kits comprising these molecules. The invention also extends to antibody-drug conjugates and to uses thereof in therapy.

Anti-ROR1 antibodies

The disclosure provides antibody agents that bind to inhibitory human killer immunoglobulin-like receptors (KIRs). Particular antibody agents of the disclosure include antibody agents that bind to KIR3DL1 (also known as CD158e). Also provided are related nucleic acids, vectors, compositions and methods of using KIR-binding antibody agents of the present technology.

Anti-KIR3DL1 antibodies

The present invention provides antigen binding proteins that specifically bind to Wilms' tumor protein (WT1), including humanized, chimeric and fully human antibodies against WT1, antibody fragments, chimeric antigen receptors (CARs), fusion proteins, and conjugates thereof. The antigen binding proteins and antibodies bind to HLA-A0201-restricted WT1 peptide. Such antibodies, fragments, fusion proteins and conjugates thereof are useful for the treatment of WT1 associated cancers, including for example, breast cancer, ovarian cancer, prostate cancer, chronic myelocytic leukemia, multiple myeloma, acute lymphoblastic leukemia (ALL), acute myeloid/myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). In more particular embodiments, the anti-WT1/A antibodies may comprise one or more framework region amino acid substitutions designed to improve protein stability, antibody binding and/or expression levels.

T cell receptor-like antibodies specific for a WTI peptide presented by HLA-A2

Disclosed herein is a bi-specific form of a T cell receptor mimic (TCRm) mAb with reactivity to human immune effector cell antigen and a WT1 peptide/HLA-A epitope. This antibody selectively bound to leukemias and solid tumor cells expressing WT1 and HLA-A as well as activated resting human T cells to release interferon-(IFN-&#x3b3;) and to kill the target cancer cells in vitro. Importantly, the antibody mediated autologous T cell proliferation and directed potent cytotoxicity against fresh ovarian cancer cells. Therapeutic activity in vivo of the antibody was demonstrated in NOD SCID SCID Yc*(NSG) mice with three different human cancers expressing WT1/HLA-A2 including disseminated Ph+ acute lymphocytic leukemia (ALL), disseminated acute myeloid leukemia, and peritoneal mesothelioma. In both of the leukemia xenograft models, mice that received the antibody and T cells also showed longer survival and delayed limb paralysis. Also provided are methods for stimulating a primary T cell response comprising stimulating cytotoxic T cells against a first tumor antigen and a secondary T cell response comprising stimulating effector T cells and/or memory T cells against a first tumor antigen and/or against a second tumor antigen using the bi-specific antibodies described herein.

Growing community of inventors

State College, PA, United States of America

Su Yan