The disclosure provides methods of treating, identifying and/or selecting for treatment a subject having a cancer in which an immune checkpoint protein is upregulated. In certain embodiments, the methods for treating cancer in a subject in need thereof comprise administering to the subject: (a) a therapeutically effective amount of an EZH2 inhibitor and (b) a therapeutically effective amount of an immune checkpoint inhibitor. In certain embodiments of the methods of the disclosure, the EZH2 inhibitor is tazemetostat.

The invention provides a polypeptide that specifically binds to CTLA-4, particularly human CTLA-4.

This disclosure relates to methods of assaying and scoring PD-L1 expression in tumors. Tumor samples are labeled with an antibody or antibody fragment that specifically binds to human PD-L1 and binding is detected. Binding intensity is compared to background, and tumor cells having membrane staining above background are counted. The percentage of tumor cells containing membrane staining of PD-L1 is determined and the tumor is classified as “PD-L1 positive” if the percentage of tumor cells falls above a predefined level.

The present invention provides therapeutic, diagnostic, and prognostic methods for cancer. The invention provides methods of treating a cancer, methods of determining whether an individual having a cancer is likely to respond to a treatment including an immune checkpoint inhibitor (e.g., a PD-L1 axis binding antagonist), methods of predicting responsiveness of an individual having a cancer to a treatment including an immune checkpoint inhibitor (e.g., a PD-L1 axis binding antagonist), methods of selecting a therapy for an individual having a cancer, methods of providing a prognosis for an individual having a cancer, and methods of monitoring a response of an individual having a cancer, based on a blood tumor mutational burden (bTMB) score or a maximum somatic allele frequency (MSAF) from a sample (e.g., a whole blood sample, a plasma sample, a serum sample, or a combination thereof) from the individual.

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.

Aspects of the present disclosure provide methods for determining the eligibility of a subject having a malignancy for treatment with an anti-PD therapeutic agent based on a Combined Positive Score (CPS) for a tumor tissue sample from the subject. Compositions and kits or performing the disclosed methods are also provided.

Described herein are novel anti-PD1 antibody reagents (e.g., antibodies, antigen-binding fragments thereof, and/or chimeric antigen receptors). Also described herein antibody-drug conjugates or kits comprising the disclosed antibody reagents, as well as methods of treating cancer by administering the disclosed antibody reagents.

The present disclosure provides a method for treating a microsatellite stable cancer patient with a specific combination of medical agents or a composition or combination therefor. Specific combinations of medical agents include a combination of a cancer stem cell inhibitor (e.g., napabucasin) and an immune checkpoint inhibitor (e.g., pembrolizumab). The MSS patient can be selected by determining if the patient has one or more patient characteristics. Another aspect of the disclosure provides a method for predicting responsiveness of a patient to a cancer treatment based on one or more patient characteristics.

Provided is an immune microbubble complex, and a use thereof. An immune-microbubble complex (IMC) according to the presently claimed subject matter includes microbubbles to which an antibody is conjugated, in which the microbubbles have excellent stability and excellent antibody binding strength, and it was confirmed that, when the immune-microbubble complex is treated with high-intensity focused ultrasound (HIFU), an anti-tumor effect is significantly increased and an immune-enhancing effect is exhibited. Therefore, the immune-microbubble complex according to the presently claimed subject matter is expected to increase the efficiency of delivering the conjugated antibody and be used in both diagnosis and treatment of cancer, and exhibit various functions in the field of immunotherapy, including a contrast effect, half-life improvement, improved drug delivery, a lymphocyte concentration effect, cancer immunotherapy and induction of immunotherapy using ultrasound.

The present disclosure provides methods of treating PD-L1 negative tumors, the methods comprising administering fusion proteins comprising the extracellular domain of human cluster of differentiation 80 (CD80) and the fragment crystallizable (Fc) domain of human immunoglobulin G 1 (IgG1).