The present invention concerns the field of oncology, and in particular tumor diagnosis for specific and tailored therapy. In particular the invention describes a method for diagnosing a tumor in a subject, said method comprising the step of performing an in vitro immunohistochemical (IHC) analysis, wherein said IHC is carried out on a fresh frozen sample and with a specific set of antibodies. The present invention further relates to a kit for IHC analysis comprising the specific panel of antibodies and instructions for use in the method of according to the invention. In a further aspect, the invention relates to the use of a kit for providing a tumor diagnosis, wherein said tumor is chosen from the group consisting of breast, liver, testis, prostate, skin (melanoma), lung, thyroid, colon, colorectal, uterus, lymph node, bladder, pancreas, spleen, upper aerodigestive tract and stomach.

Provided herein are methods for detecting a target moiety in a biological sample suspected of containing the target moiety, by incubating the biological sample with an antibody and a fusion polypeptide, the fusion polypeptide comprising (i) an immunoglobulin-binding polypeptide and (ii) a reporting species.

The disclosure relates to the use of biomarkers for predicting the response to cancer (e.g., melanoma) treatments, for selecting a treatment for a cancer patient (e.g., using targeted therapy, e.g., using an agent targeting BRAF and/or an agent targeting MEK in combination with an immuno-oncology therapy (e.g., an anti-PD-1 therapy)), for stratifying cancer patients into different treatment groups, for treating cancer patients, and for predicting clinical outcome in cancer.

The present disclosure relates to the detection of beta amyloid protein as an Alzheimer's disease-causing factor in the palatine tonsil and a use thereof and, more specifically, to the diagnosis of Alzheimer's disease by identifying the expression of beta amyloid and/or Staphylococcus aureus in a tonsillar sample. The present disclosure can diagnose Alzheimer's disease through the expression of beta amyloid and/or Staphylococcus aureus in a palatine tonsil tissue and, furthermore, can be very advantageously used for revealing the pathogenesis of Alzheimer's disease and for treating Alzheimer's disease.

Provided are methods for treating cancer by converting tumor-resident macrophages into a hybrid M1/M2 macrophage phenotype; this phenotype has attributes that are advantageous for cancer therapy. Hybrid markers include (lower than M2, higher than M1): SPP1, CD209, and CD206, and induced markers include MERTK, C1QC, IFNa, IFNb, CXCL10, 4-1BBL, and MYC. The methods include administering a therapeutic that effects the phenotypic conversion. Therapeutics, such as delivery vehicles, including immunostimulatory bacteria with genome modifications, are designed so that they do not induce or result in a sufficient TLR2, TLR4, TLR5 response to inhibit type I IFN. The therapeutics also encode a payload that encodes immunostimulatory proteins, such as a cytokine and a modified cytosolic DNA/RNA sensor that constitutively induces type I IFN, such as a modified STING protein. The combination of payload immunostimulatory proteins and properties of the therapeutic delivery vehicle, upon administration, results in macrophage with the hybrid phenotype. The therapeutics are administered to subjects identified as having tumors that comprise proliferating M2 macrophages.

The present disclosure provides TGF? inhibitor therapy for treating immunosuppressive conditions, cancer, and fibrosis, either as a monotherapy or combination/adjunct therapy. Selection of suitable therapy and patients who are likely to benefit from such therapy are also disclosed, as well as methods of treating cancer and fibrosis and methods of predicting and monitoring therapeutic response. Related compositions, methods and therapeutic use are also disclosed.

In alternative embodiments, provided are immunohistochemistry (IHC) methods for determining and scoring reproducibly the extent of nuclear expression of protein Ki-67 (also known as MK167) in a tissue sample. In alternative embodiments, provided are methods for diagnosing, treating or ameliorating or assessing the risk of recurrence for a cancer or a tumor using an IHC method as provided herein. In alternative embodiments, provided are kits comprising components and instructions for practicing methods as provided herein.

A method for detecting the amount of CDH17 protein in a sample from Automated Tissue Staining a subject, the method comprising: contacting the sample with a buffer at a temperature of at least 98 C. to provide a treated sample, contacting the treated sample with a capture antibody having a binding affinity to CDH17, wherein any exposed CDH17 expressing epitope in the treated sample is configured to bind to the capture antibody to provide a bound sample, contacting the bound sample with a detection molecule to provide a detection sample, wherein the detection molecule comprises a biocompatible enzyme conjugated to a secondary antibody having a binding affinity to the capture antibody, reacting the detection sample with a 3,3Diamonobenzidine chromogen to provide an oxidized substrate, and determining the amount of CDH17 protein in the sample based on the amount of oxidized substrate.

Methods, systems, compositions, and thermochemical processes for inactivating proteinaceous binding entities (PBEs) such as antibodies in between staining cycles for preventing cross-reactivity in subsequent staining cycles. The thermochemical methods, compositions, or systems may feature incubating a sample in a solution comprising a buffer at a temperature sufficient to reduce or eliminate further detectability of the PBE. The methods, compositions, and systems may be beneficial for automated assays in automated staining devices that are adapted to dispense buffers and reagents and to heat samples to various temperatures.

In alternative embodiments, provided are non-natural synthetic antibodies capable of specifically binding a human CD10 polypeptide, or neprilysin, polypeptide. In alternative embodiments, also provided are products of manufacture and kits comprising antibodies as provided herein, and methods for making and using antibodies as provided herein, where the antibodies can be used for in vitro diagnostics by immunohistochemistry (IHC). In alternative embodiments, antibodies as provided herein are used in IHC protocols to diagnose a cancer, for example, leukemic cell cancer of pre-B phenotype, acute lymphoblastic leukemia (ALL), angioimmunoblastic T cell lymphoma, Burkitt lymphoma, chronic myelogenous leukemia in blast crisis, diffuse large B-cell lymphoma, hairy cell leukemia, myeloma, precursor B lymphoblastic leukemia or lymphoma, follicular lymphoma, mantle cell lymphoma, precursor T lymphoblastic leukemia or lymphoma, non-hematolymphoid sarcoma, or carcinoma such as renal cell carcinoma or metaplastic breast carcinoma.