The present invention relates to a method for inhibiting intracellular activated RAS using an intact immunoglobulin-type antibody having the ability to penetrate the cytosol. The present invention also relates to a heavy-chain variable region (VH) which induces an intact immunoglobulin-type antibody to actively penetrate the cytosol of living cells through endocytosis and endosomal escape and to bind to activated RAS in the cytosol, and to an antibody comprising the same. The present invention also relates to a method of inhibiting the growth of cancer or tumor cells and a method of treating cancer or tumor, by use of the antibody. The present invention also relates to a method for screening a heavy-chain variable region that binds specifically to RAS in the cytosol. The present invention also relates to a biologically active molecule fused to the antibody and selected from the group consisting of peptides, proteins, small-molecule drugs, nanoparticles and liposomes. The present invention also relates to a composition for prevention, treatment or diagnosis of cancer, comprising: the antibody; or a biological active molecule fused to the antibody and selected from the group consisting of peptides, proteins, small-molecule drugs, nanoparticles and liposomes. The present invention also relates to a polynucleotide that encodes the light-chain variable region and the antibody.

According to the present invention, the method for inhibiting intracellular activated RAS using an intact immunoglobulin-type antibody having the ability to penetrate the cytosol is achieved by allowing the antibody to penetrate living cells and to specifically recognize activated (GTP-bound) RAS in the cytosol. Thus, the antibody can target activated (GTP-bound) RAS in the cytosol of living cells and inhibit the activity of the RAS.

Furthermore, the antibody light-chain variable region according to the present invention and an antibody comprising the same is able to penetrate living cells and localize in the cytosol, without having to use a special external protein delivery system. Particularly, the antibody light-chain variable region according to the present invention can easily interact with various human heavy-chain variable regions (VHs) and has the ability to penetrate the cytosol and remain in the cytosol, and an intact IgG-type monoclonal antibody comprising the light-chain variable region can penetrate cells and localize in the cytosol, and shows no cytotoxicity non-specific for target cells.

The antibody heavy-chain variable region according to the present invention and an antibody comprising the same can selectively inhibit mutations of the major drug resistance

A cell response assay for cancer is provided. In the assay, the levels of a cancer cell type biomarker, a chemo resistance biomarker and a metastatic potential biomarker are simultaneously measured in a biological sample.

The present disclosure provides antigen-binding proteins which bind to Claudin-6 (CLDN6). In various aspects, the antigen-binding proteins bind to Extracellular Loop 2 (EL2) of the extracellular domain of CLDN6. Related polypeptides, nucleic acids, vectors, host cells, and conjugates are further provided herein. Kits and pharmaceutical compositions comprising such entities are moreover provided. Also provided are methods of making an antigen-binding protein and methods of treating a subject having cancer.

Isolated monoclonal antibodies which bind to human c-Met, the hepatocyte growth factor receptor, and related antibody-based compositions and molecules, are disclosed. Pharmaceutical compositions comprising the antibodies and therapeutic and diagnostic methods for using the antibodies are also disclosed.

There has been a recent shift in cancer therapy from one size fits all to a personalized and tailored treatment for individual patients to increase efficiency and avoid unnecessary toxicity. This invention relates to a method of determining the prognosis and suitable treatment of cancer in a subject by measuring the level of expression of SPAG5. In particular, it relates to a method where high expression of SPAG5 in tumour cells correlates with aggressive tumors.

Truncation variants of BCR-ABL mRNA that produces BCR-ABL proteins with a truncated C-terminus and its role in resistance to treatment with kinase inhibitors is described. Vectors for expressing the truncated gene products are described as well as recombinant cells that express the truncated gene products from cDNA constructs. Also provided are methods compositions and kits for detecting the BCR-ABL truncation variants. Also provided are methods for determining the prognosis of a patient diagnosed as having myeloproliferative disease, and methods for predicting the likelihood for resistance to a treatment with tyrosine kinase inhibitor in a patient diagnosed as having myeloproliferative disease. Additionally, methods for screening BCR-ABL tyrosine kinase domain inhibitors which rely on the recombinant cells are also disclosed.

The invention provides to RAF1 gene fusions, RAF1 fusion proteins, and fragments of those genes and polypeptides. The invention further provides methods of diagnosing and treating diseases or disorders associated with RAF1 fusions, such as conditions mediated by aberrant RAF1 expression or activity, or overexpression of RAF1.

The presently disclosed subject matter relates to the use of one or more biomarkers to evaluate the likelihood that an EZH2 inhibitor would produce an anti-cancer effect in a subject. It is based, at least in part, on the discovery that loss of BAP1 results in the upregulation of EZH2 expression and activity. In a specific non-limiting embodiment, the method comprises obtaining a sample of the cancer from a subject, and determining, in the sample, the expression level of an BAP1 biomarker, where if the BAP1 biomarker is absent or expressed at lower level in the cancer as compared to a reference control level, then administering a therapeutically effective amount of an EZH2 inhibitor to produce an anti-cancer effect.

The technology described herein is directed to methods, assays, and systems relating to determining the level of SAKT signaling activity in a sample obtained from a subject as well as methods relating to administering inhibitors and/or agonists of SAKT signaling.

The present invention relates to an immunoassay method for the detection of Chromogranin A (or fragment(s) thereof) comprising the steps of contacting a sample suspected of comprising Chromogranin A with a first antibody or an antigen-binding fragment or derivative thereof specific for Chromogranin A and a second antibody or an antigen-binding fragment or derivative thereof specific for Chromogranin A under conditions allowing for the formation of a ternary complex between Chromogranin A and the two antibodies or antigen-binding fragments or derivates thereof, and detecting the binding of the two antibodies or antigen-binding fragments or derivates thereof to Chromogranin A. Also provided are antibodies directed against amino acid residues 124 to 144 and 280 to 301 of Chromogranin A and their use in the immunoassay method.