The present invention relates to a use of an endothelin receptor inhibitor for inhibiting exosome secretion or inhibiting PD-L1 expression. It was confirmed that the endothelin receptor inhibitor inhibits endothelin receptors, which are currently known as a target for anticancer drug development, to not only inhibit the secretion of cancer cell-derived exosomes, but also reduce the expression of PD-L1 in cells, and is thus effective for cancer treatment when used in combination with existing anticancer drugs or when used alone in the form of a drug. Accordingly, the present invention can be used in novel modes of anticancer drug development using drugs exhibiting immune-checkpoint inhibition effects and exosome secretion inhibition effects.

Provided is a complementary determining region (CDR) of a VHH chain of an anti-PD-L1 single-domain antibody, wherein the CDR of the VHH chain includes the following: CDR1 with an amino acid sequence as shown in SEQ ID NO:5n+1; CDR2 with an amino acid sequence as shown in SEQ ID NO:5n+2, or CDR2 with an amino acid sequence having an sequence identity of greater than 85% with a sequence as shown in SEQ ID NO:2; and CDR3 with an amino acid sequence as shown in SEQ ID NO: 5n+3; wherein, each n is independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15.

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.

The invention provides biomarkers for predicting the response to checkpoint inhibitors. The inventors demonstrate that a PD-1/PD-L1 inhibitor exerts antitumor activity against tumor with low PD-L1 expression and immune-desert phenotype through blocking PD-L1 in the lymph nodes. The invention provides novel combinations of intratumoral markers for antigen cross-presenting cells and T cell chemokines which are expected to be superior efficacy-predicting biomarkers compared to existing methods.

A PD-L1 nano-antibody and a PD-L2 nano-antibody, and a bispecific antibody having both the PD-L1 nano-antibody and the PD-L2 nano-antibody are disclosed. The bispecific antibody can block PD-1/PD-L1 and PD-1/PD-L2 pathways at the same time. The bispecific antibody can reactivate T cells, enhance immune responses, and more effectively improve the inhibitory effect on tumor occurrence and development.

The present disclosure provides novel macrocyclic peptides which inhibit the PD-1/PD-L1 and PD-L1/CD80 protein/protein interaction, and thus are useful for the amelioration of various diseases, including cancer and infectious diseases.

This document features methods of evaluating mammals by assessing expression of B7-H1 in a body fluid.

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.

A B7-H3 antibody, an antigen-binding fragment thereof and a medical use thereof are provided. Furthermore, a pharmaceutical composition containing the B7-H3 antibody or antigen-binding fragment thereof, and the use thereof as a medicament are provided. In particular, a use of a human B7-H3 antibody or antigen-binding fragment thereof for the manufacture of a medicament for the treatment of a B7-H3-associated disease or condition are described.

Disclosed are compositions, methods, apparatus and kits that take advantage of peripheral blood biomarkers for diagnosing and/or monitoring the Th1 immune status of a subject. In particular, the methods, apparatus and kits are useful for diagnosis, monitoring, making treatment decisions, or management of subjects suspected of having Th1-related disease.