This disclosure relates to binding agents with specificity for programmed cell death 1 (PD-1) and to methods for using the same to treat, prevent and/or ameliorate an infectious disease (e.g., human immunodeficiency virus (HIV)), cancer and/or autoimmunity. In addition, this disclosure identifies a novel binding patch (“P2”) on PD-1 that is linked with a previously unidentified functional activity of PD-1 that is distinct from the interaction site involved with either the PD-L1 or PD-L2 ligands. Furthermore, we demonstrate that antibodies that interact with this region of PD-1 are able to act as antagonists of PD-1 and that this antagonism is further enhanced with the addition of antibodies that act through the blockade of the PD-1/PD-L1/L2 interaction.

Antibodies that selectively bind to glycosylated PD-1 relative to unglycosylated PD-1 are provided. In some aspects, PD-1 polypeptides comprising glycosylated amino acid positions are also provided. Methods for making and using such antibodies and polypeptides (e.g., for the treatment of cancer) are also provided.

Provided herein are biomarkers for the treatment of pathological conditions, such as cancer, and method of using PD-1/PD-L1 pathway antagonists. In particular, provided are biomarkers for patient selection and prognosis in cancer, as well as methods of therapeutic treatment, articles of manufacture and methods for making them, diagnostic kits, methods of detection and methods of advertising related thereto.

The present invention relates to means and methods for determining whether a patient is in need of a PD-L1 inhibitor cotherapy. A patient is determined to be in need of the PD-L1 inhibitor cotherapy if a low or absent ER expression level and an expression level of programmed death ligand 1 (PD-L1) that is increased in comparison to a control is measured in vitro in a sample from the patient. The patient is undergoing therapy comprising a modulator of the HER2/neu (ErbB2) signaling pathway (like Trastuzumab) and a chemotherapeutic agent (like dodetaxel) or such a therapy is contemplated for the patient. Also provided herein are means and methods for treating a cancer in a cancer patient for whom therapy comprising a modulator of the HER2/neu (ErbB2) signaling pathway (like Trastuzumab) and a chemotherapeutic agent (like dodetaxel) is contemplated, wherein the patient is to receive PD-L1 inhibitor cotherapy.

Provided are anti-PD-L1 antibodies, variants, mutants, and antigen binding fragments thereof. Also provided are isolated nucleic acid molecules that encode the anti-PD-L1 antibodies, variants, mutants, or antigen binding fragments thereof, and related expression vectors, and host cells. Provided are methods of making anti-PD-L1 antibodies, variants, mutants, and antigen binding fragments thereof. Also provided are related pharmaceutical compositions and methods of their use to treat subjects. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

Provided is an anti-PD-L1 monoclonal antibody. The antibody can be used to prepare a drug for preventing or treating a disease related to PD-L1.

Methods are provided for assaying bladder-associated samples. Aspects of the methods include detecting per cell programmed-death ligand 1 (PD-L1) expression in a bladder-associated sample. In some instances, the methods include detecting whether an immune cell that expresses PD-Ll above a predetermined threshold is present in a bladder-associated sample and/or detecting a PD-L1-aneuploid-to-PD-L1-epithelial ratio of a bladder-associated sample. Aspects of the methods may also include identifying whether a malignant bladder-associated neoplasia is present. Methods are also provided for treating a subject for a malignant bladder-associated neoplasia, wherein aspects of such methods include administering a therapeutic to a subject having an identified malignant bladder-associated neoplasia. In addition, kits that find use in practicing the subject methods are also provided.

The present invention provides therapeutic and diagnostic methods and compositions for cancer, for example, non-small cell lung cancer (NSCLC). The invention provides methods of treating NSCLC, methods of determining whether a patient suffering from NSCLC is likely to respond to treatment comprising a PD-L1 axis binding antagonist, methods of predicting responsiveness of a patient suffering from NSCLC to treatment comprising a PD-L1 axis binding antagonist, and methods of selecting a therapy for a patient suffering from NSCLC, based on expression levels of a biomarker of the invention (e.g., PD-L1 expression levels in tumor cells and/or tumor-infiltrating immune cells).

A method for simultaneously detecting an exosome membrane protein and mRNA is provided. The method can perform simultaneous detection on exosomes separated and purified from the same sample by labeling an exosome membrane protein with a fluorescent antibody and labeling a target gene mRNA with a molecular beacon, wherein labeling the exosome with the molecular beacon is specifically performed by means of an in-situ exosome capture well plate or chip, and each well or chip in the in-situ exosome capture well plate includes a fluorescein-labeled molecular beacon; and the molecular beacon is a specific DNA probe for detecting the target gene mRNA. The present invention utilizes an in-situ exosome capture well plate or chip technology to detect a biomarker gene mRNA contained in an exosome of a biological sample.

Provided in the present disclosure are a method for providing information on a therapeutic reaction of cancer immunotherapy and a kit using same for providing information, the method comprising the steps of: measuring respective expression levels of PD-L1 and PVR in a biological sample isolated from a subject; and evaluating the therapeutic reaction of cancer immunotherapy for the subject on the basis of the measured expression levels of PD-L1 and PVR.