The present invention provides methods for the production of a library of antigen specific antigen binding molecules having a peptide domain structure represented by the following formula (I): FW 1-CDR1-FW2-HV2-FW3a-HV4-FW3b-CDR3-FW4 comprising (1) isolating RNA from a member of a species in the Elasmobranchii subclass; (2) amplifying DNA sequences from RNA obtained; (3) selecting a DNA sequence from the database prepared; (4) amplifying DNA sequences encoding two or more contiguous peptide domains of FW1-CDR1-FW2-HV2-FW3a-HV4-FW3b-CDR3-FW4; (5) ligating together said amplified DNA sequences to form DNA sequences encoding an antigen specific binding molecule; (6) cloning the amplified DNA obtained into a display vector; and (7) transforming a host with said display vector to produce a library of said antigen specific antigen binding molecules. The invention also provides methods for the production of an antigen specific antigen binding molecule as defined, pharmaceutical compositions comprising such molecules and uses thereof in medicine.

The invention provides a method of treating a melanoma comprising (i) identifying a patient having a PD-L1 positive melanoma and (ii) administering to the patient an anti-PD-1 antibody or an antigen-binding portion thereof (“an anti-PD-1 antibody monotherapy”). The methods of the invention can extend progression-free survival for over 12 months and/or reduces the tumor size at least about 10%, about 20%, about 30%, about 40%, or about 50% compared to the tumor size prior to the administration.

The present invention relates to anti-PD-L1 binding members and in particular to monovalent, high potency PD-L1-binding antibody fragments being highly stable and soluble. Such binding members may be used in the treatment of cancer and inflammatory diseases as well as in diagnostics. Also provided are related nucleic acids, vectors, cells, and compositions.

This disclosure relates to synthetic ligands for detecting PD-L1 in a sample or subject. The ligand can be labeled with a variety of detectable labels allowing of visualization and quantification. The ligand provides an alternative PD-L1 binding molecule with advantages over current antibody technologies for detecting PD-L1.

A method for identifying a patient with malignant tumor which can be expected to benefit more from an immune checkpoint inhibitor, and agent for suppressing the progression of, suppressing the recurrence of, and/or treating malignant tumor, being prescribed based thereon, comprising use of a combination of two sets of evaluation items and specific condition defined by each of combination thereof.

Methods of using detection of PD-L1 expression by circulating cancer cells in the screening, monitoring, treatment and diagnosis of cancer in subjects are disclosed. The methods are based on assaying one or more of circulating tumor cells (CTCs), epithelial to mesenchymal transition CTCs (EMTCTCs), cancer associated macrophage-like cells (CAMLs), and cancer associated vascular endothelial cells (CAVEs) isolated from a subject having cancer for PD-L1 expression.

The present invention is based on the identification of novel biomarkers predictive of responsiveness to anti-immune checkpoint therapies.

Provided herein are methods of treating cancer in a subject including detecting an amount of PD-L1(+) natural killer (NK) cells in a biological sample from the subject and treating the subject with an anti cancer therapy. Provided herein are methods of treating cancer in a patient including isolating natural killer (NK) cells from a subject, producing a population of PD-L1(+) NK cell from the isolated NK cells, and administering the population of PD-L1(+) NK cells into the patient.

The present invention relates to the field of inflammation. More specifically, the present invention provides compositions and methods for treating cerebral inflammation and associated sequelae thereof including cerebral vasospasm. In one embodiment, a method for treating cerebral vasospasm in a patient comprises the step of administering to the patient a PD-1 agonist, wherein a blood sample obtained from the patient comprises elevated PD-1 expression on monocytes relative to a control.

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.