The present invention provides diagnostic methods, therapeutic methods, and compositions for the treatment of cancer (e.g., kidney cancer (e.g., renal cell carcinoma (RCC)), lung cancer (e.g., non-small cell lung cancer (NSCLC)), bladder cancer (e.g., urothelial bladder cancer (UBC)), liver cancer (e.g., hepatocellular carcinoma (HCC)), ovarian cancer, or breast cancer (e.g., triple-negative breast cancer (TNBC))). The invention is based, at least in part, on the discovery that expression levels of one or more biomarkers described herein in a sample from an individual having cancer can be used in methods of predicting the therapeutic efficacy of treatment with a VEGF antagonist (e.g., an anti-VEGF antibody, (e.g., bevacizumab) or a VEGFR inhibitor (e.g., a multi-targeted tyrosine kinase inhibitor (e.g., sunitinib, axitinib, pazopanib, or cabozantinib))) and a PD-L1 axis binding antagonist (e.g., a PD-L1 binding antagonist (e.g., anti-PD-L1 antibody, e.g., atezolizumab (MPDL3280A)) or a PD-1 binding antagonist (e.g., anti-PD-1 antibody)), or with an angiogenesis inhibitor (e.g., a VEGF antagonist (e.g., a VEGFR inhibitor, (e.g., a multi-targeted tyrosine kinase inhibitor (e.g., sunitinib, axitinib, pazopanib, or cabozantinib)))).

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

Monoclonal antibodies that bind glypican-2 (GPC2) with high affinity are described. Immunotoxins and chimeric antigen receptors (CARs) that include the disclosed antibodies or antigen-binding fragments thereof are further described. In some instances, the antibody or antigen-binding fragment is humanized. The disclosed GPC2-specific antibodies and conjugates can be used, for example, for the diagnosis or treatment of GPC2-positive cancers, including neuroblastoma, medulloblastoma and retinoblastoma.

Disclosed herein are a method and a biomarker for predicting efficacy and prognosis of or resistance to an immunotherapy. The use of the biomarkers (TCTP, EGFR, AKT, MCL1, and/or CXCL10) of the present disclosure allows the prediction of resistance to or prognosis of a cancer immunotherapeutic agent and the selection of a therapy guaranteeing therapeutic benefit, thereby finding advantageous applications in treating cancers or tumors resistant to cancer immunotherapeutic agents.

Disclosed are compounds, for example, a compound of formula I, wherein R, R.sub.0, R.sub.1-R.sub.8, n, X, Y, Y, and E are as described herein, pharmaceutical compositions containing such compounds, and methods of treating or preventing a disease or condition for example, cancer, mediated by the ras gene.

##STR00001##

A method for the detection and/or diagnosis of cancer in a patient is disclosed. The method involves detecting circulating tumor cells (CTCs) in a sample obtained from the patient using an antibody specifically binding to an antigen in a protein expressed by the CTCs, wherein the antigen comprises a mutation and wherein the mutation renders the patient receptive or resistance to an anti-cancer drug. Claimed methods include the use of an antibody specific for the EGFR L858R or EGFR exon 19 (E746-A750) mutations for detecting lung cancers and the use of an antibody specific for the K-Ras G12V, K-Ras G12C, K-Ras G12S, K-Ras G12D, or K-Ras G13D mutations for detecting colorectal cancers.

The present disclosure relates to the field of immunotherapy of cancer, in particular pancreatic ductal adenocarcinoma (PDAC). Means and methods for treatment of a population of PDAC patients suffering from PDAC tumours which express wildtype KRAS, HRAS or NRAS are disclosed. The claimed antibody is Nimotuzumab. The pancreatic cancer preferably does not contain KRAS mutations at position 12, 16, 61, 154.

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.

Cyclic peptides represented by (Formula 1) ##STR00001##
selectively bind the oncoprotein K-Ras G12D in vitro and in cellulo, where Z1 and Z2 are each L-propargylglycine (Pra), azidoornithine (OrnN3), or L-azidolysine (Az4), and V1-V2-V3-V4-V5 is an amino acid variable region having a sequence selected from the group consisting of SEQ ID NOs: 1-20.