Abstract: The present invention relates to Chimeric Antigen Receptors (CAR) that are recombinant chimeric proteins able to redirect immune cell specificity and reactivity toward selected membrane antigens, and more particularly in which extracellular ligand binding is a scFV derived from a 5T4 monoclonal antibody, conferring specific immunity against 5T4 positive cells. The engineered immune cells endowed with such CARs are particularly suited for treating lymphomas and leukemia, and for solid tumors such as colon, stomach, and ovarian tumors.

Abstract: The present invention relates to bispecific chimeric polypeptide assembly compositions comprising bulking moieties linked to binding domains by cleavable release segments that, when cleaved are capable of concurrently binding effector T cells with targeted tumor or cancer cells and effecting cytolysis of the tumor cells or cancer cells. The invention also provides compositions and methods of making and using the cleavable chimeric polypeptide assembly compositions.

Abstract: Disclosed herein are B cell maturation antigen binding proteins with improved binding affinities and improved ability to mediate killing of cancer cells expressing B cell maturation antigen (BCMA). Pharmaceutical compositions comprising the binding proteins disclosed herein and methods of treatment of a cancer or a metastasis thereof using such formulations are further provided.

Abstract: The present invention relates to compositions and methods for treating diseases, disorders or conditions associated with the expression of the Glycosyl-phosphatidylinositol (GPI)-linked GDNF family ?-receptor 4 (GFR?4).

Abstract: Method of selecting treatment for a subject diagnosed with cancer comprises contacting antibody that binds specifically to thymidine kinase 1 (TK1) protein with a first body fluid sample before completing cancer treatment; determining a first amount of antibody binding to TK1 protein in the first sample; correlating the first amount to a first concentration of TK1 protein using a standard curve correlating an amount of antibody binding to recombinant human TK1 (rhTK1) and a concentration of rhTK1; contacting the antibody with a second body fluid sample within one to six months after the cancer treatment; determining a second amount of antibody binding to TK1 protein in the second sample; correlating the second amount to a second concentration using the curve; identifying the patient as having a high risk of future cancer relapse if the second concentration is ? the first concentration; and selecting an adjuvant treatment based on the identification.

Abstract: Disclosed are compositions and methods for targeted treatment of CLEC12A-expressing cancers. In particular, chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer to target and kill CLEC12A-expressing cancers. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with a CLEC12A-expressing cancer that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs. Also disclosed are multivalent antibodies are disclosed that are able to engage T-cells to destroy CLEC12A-expressing malignant cells.

Abstract: An antibody-drug conjugate (ADC) or a pharmaceutically acceptable salt thereof, is provided. The ADC includes a tetravalent monoclonal antibody conjugated to a cytotoxic drug by a chemical linker. The monoclonal antibody includes two long chains and four short chains. Each of the long chains includes a first segment and a second segment, the first segment located proximal to the N-terminus of the long chain, and the second segment located proximal to the C-terminus of the long chain. Each of the first segment and second segment pairs with one of the short chains to form an antigen-binding fragment domain, therefore forming four antigen-binding fragment domains having specificity toward the same antigen. Pharmaceutical composition including the ADC and methods of treating diseases using the compositions are also provided.

Abstract: The present invention relates to a switch molecule for activating a chimeric antigen receptor effector cell, to a polypeptide or fusion protein binding thereto, and to a chimeric antigen receptor. (i) When a switch molecule of the present invention is used, in order to improve safety of a CAR-T cell, if severe toxicity appears, a switch molecule lacking a targeting moiety can be injected to adjust activation of the CAR-T cell. (ii) When an antigen is mutated, or in order to cure various carcinomas, instead of an existing switch molecule, a switch molecule targeting a new antigen generated due to the mutation or a switch molecule targeting a different tumor associated antigen (TAA) can be injected into a patient to cure cancer more effectively.

Abstract: The invention provides means and methods for inhibiting growth of a cancer. The means in some embodiments comprise proteins and antibodies that binds an extracellular part of a membrane associated member of the epidermal growth factor (EGF) receptor family and an extracellular part of a membrane associated member of a WNT signaling pathway. Further provided are various cells and assays that are helpful in the production of the proteins, antibodies and cells.

Abstract: The present invention provides a therapeutic agent for the treatment, prevention and diagnosis of cancers associated with cells that overexpressing transferrin receptor 1 (TfR1) and its variants on the cell surface, including but not limited to AML, ALL, lymphoma, multiple myeloma, breast cancer, gastric cancer, glioblastoma, prostate cancer, urothelial bladder cancer, pancreatic cancer, esophageal cancer, colorectal cancer, ovarian cancer, liver cancer. The agent is based on the amino acid sequences of the novel light chain and heavy chain variable regions of an anti-TfR1 monoclonal antibody (mAb), MAb11-22.1, which, is highly specific for tumor cells and in an ADC form, can functionally inhibit the proliferation of several human cancer cell lines and the growth of AML cell line-derived xenograft tumors in mouse models.

Abstract: The invention provides a method of inhibiting angiogenesis in an individual, the method comprising administering to the individual an agent that inhibits the interaction between CLEC14A and MMRN2. The inhibitor may be an antibody, a polypeptide, a peptide, a polynucleotide, a peptidomimetic, a natural product, a carbohydrate, an aptamer or a small molecule.

Abstract: Provided herein are compositions, methods and uses involving antibodies that specifically bind to MET, a receptor tyrosine kinase, and modulate the expression and/or activity of MET. Also provided are uses and methods for managing, treating, or preventing disorders, such as cancer. In one aspect, provided herein is a monoclonal antibody or antigen-binding fragment thereof that binds to the Sema/PSI domain of human MET. Also provided herein is a kit comprising an antibody or antigen-binding fragment provided herein. Also provided herein is a method of managing, protecting against, or treating cancer in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of an antibody or antigen-binding fragment provided herein.

Abstract: The presently disclosed subject matter provides for methods and compositions for treating multiple myeloma. It relates to chimeric antigen receptors (CARs) that specifically target a G-protein coupled receptor (e.g., a G-protein coupled receptor family C group 5 member D (GPRC5D)), and immunoresponsive cells comprising such CARs. The presently disclosed CARs targeting a G-protein coupled receptor (e.g., GPRC5D) have enhanced immune-activating properties, including anti-tumor activity.

Abstract: Antigen binding fragments, chimeric antigen receptors, and bi-specific T-cell engagers having specificity for MICA and methods for using the same in the diagnosis and treatment of disorders associated with MICA and/or MICB expression are provided.

Abstract: Embodiments relate to a modified cell comprising a polynucleotide encoding a dominant negative form of Death receptor 5 (DR5). In embodiments, the modified cell further comprises a chimeric antigen receptor (CAR) and/or a modified TCR.

Abstract: The presently disclosed subject matter provides for methods and compositions for treating multiple myeloma. It relates to chimeric antigen receptors (CARs) that specifically target a G-protein coupled receptor (e.g., a G-protein coupled receptor family C group 5 member D (GPRC5D)), and immunoresponsive cells comprising such CARs. The presently disclosed CARs targeting a G-protein coupled receptor (e.g., GPRC5D) have enhanced immune-activating properties, including anti-tumor activity.

Abstract: Antibodies, fragments thereof, and chimeric proteins comprising same are presented that have specific binding activity against CD30. Advantageously, contemplated molecules can be used in pharmaceutical compositions for immune therapy, particularly in individuals diagnosed with hematopoietic malignancies, including Hodgkin lymphoma, CD30-positive B cell lymphomas, CD30-positive T cell lymphomas, CD30-positive NK cell lymphomas.

Abstract: Provided herein are NK-92 cells expressing at least one CAR and at least one Fc receptor. Also provided are methods of treatment of a patient having or suspected of having a disease that is treatable with NK-92 cells, such as cancer, comprising administering to the patient NK-92-Fc-CAR.

Abstract: As disclosed herein, stapled peptides targeting the interaction interface between proteins that maintain the integrity of Wiskott-Aldrich syndrome protein family member 3 (WASF3) leads to destabilization of WASF3 and suppression of invasion. Disclosed are stapled peptides that inhibit the binding of Cytoplasmic FMR1-interacting protein 1 (CYFIP1) to either WASF3 or NCK-associated protein (NCKAP1). Also disclosed are methods for treating or suppressing invasion and metastasis of a cancer in a subject that involve administering to the subject a therapeutically effective amount of a stapled peptide disclosed herein.

Abstract: The present invention provides vaccines comprising carbohydrate antigen conjugated to a diphtheria toxin (DT) as a carrier protein, wherein the ratio of the number of carbohydrate antigen molecule to the carrier protein molecule is higher than 5:1. Also disclosed herein is a novel saponin adjuvant and methods to inhibit cancer cells, by administering an effective amount of the vaccine disclose herein.