Materials and methods for treating potentially chemoresistant tumors (e.g., using DNA-PKcs inhibitors and anti-B7-H1 antibodies) are provided herein.

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.

Embodiments of the disclosure include methods and compositions directed to targeting of cells that express the long form of Bone marrow stromal cell antigen 2 (BST2) protein, including cancer cells that express the long isoform of BST2. In particular embodiments, monoclonal antibodies or functionally active fragments thereof are utilized to target cells that express the long isoform of BST2. The monoclonal antibodies or functionally active fragments thereof may be utilized by themselves or as part of other entities, such as cells or engineered antigen receptors. The disclosure includes methods of treatment, prevention, and/or diagnosis using the encompassed antibodies or functional fragments thereof.

Provided are methods for detecting or isolating circulating tumor cells (CTCs) in a subject. The methods may include detecting the expression of at least one epithelial mesenchymal transition (EMT) biomarker. Further provided are kits for detecting or isolating CTCs. The kits may include antibodies to at least one EMT biomarker. Further provided are methods of predicting the responsiveness of a subject to a cancer drug, methods of targeting delivery of a cancer drug in a subject, methods of providing a cancer prognosis to a subject, and methods for following the progress of cancer in a subject.

A method of diagnosing a cancer or a pre-malignant lesion is disclosed. The method comprising determining a level of expression of CD24 on leukocytes comprised in a biological sample of a subject, wherein a level of CD24 on small leukocytes and not on large leukocytes above a predetermined threshold is indicative of the cancer or the pre-malignant lesion. A method of monitoring efficacy of cancer therapy and a kit for diagnosing a cancer or a pre-malignant lesion are also disclosed.

The present invention provides methods of testing anti-STn antibodies for their ability target cancer stem cells by isolating cancer stem cells from cultures, contacting them with anti-STn antibodies being tested, and measuring resulting cell viability.

The present invention relates to a method for diagnosing Sézary syndrome or mycosis fungoides in a subject. The present invention further relates to a method for determining the frequency of Sézary signature cells and/or mycosis fungoides cells in a sample. Further, the present invention relates to a computer-implemented method comprising a classifier algorithm to determine the frequency of Sézary signature cells and/or mycosis fungoides cells. In addition the present invention relates to a panel of biomarkers that can be used for the diagnosis of Sézary syndrome or mycosis fungoides.

Embodiments disclosed herein provide a peptoid compound comprising a structure shown in Formula I and a detection chip having the peptoid compound coupled onto its surface. The peptoid compound has a strong binding ability with EpCAM protein on the surface of circulating tumor cells. The diagnostic technology of colorectal adenocarcinoma, gastric adenocarcinoma, breast cancer, ovarian cancer, lung adenocarcinoma, prostate cancer, pancreatic cancer, stem cell cancer, retinoblastoma, or primary esophageal squamous cell carcinoma based on the peptoid compound can realize rapid detection or diagnosis. In addition, the peptoid compound can be made by a simple synthesis method with high preparation efficiency and low production cost.

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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 invention is based on the identification of the intracellular kinase calcium/calmodulin-dependent protein kinase 1D (CAMK1D) as a key checkpoint inhibitor in tumour cells mediating resistance against cytotoxic T lymphocytes (CTL). CAMK1D was identified in PD-L1 refractory tumours to impair CTL-induced death receptor signalling and apoptosis via caspase inhibition. The invention offers therapeutic approaches involving impairing CAMK1D immune checkpoint function by various CAMK1D inhibitors, especially nucleic acid or small molecule inhibitors of CAMK1D and/or treatments involving CAMK1D inhibitors with death receptor agonists. The medical approaches of the invention are useful for treating subjects suffering from various proliferative disorders; preferably such proliferative disorders that are characterized by a resistance to CTL mediated immune responses, or which are refractory or resistant to treatments with other immune checkpoint therapies, such as PD1-PDL1 antagonistic treatments. Provided are the medical applications and corresponding diagnostic approaches, kits, CAMK1D inhibitors and screening methods for the identification of new therapeutic agents for the treatment of proliferative disorders.