Abstract: Antibodies that selectively bind to glycosylated LAG3 relative to unglycosylated LAG3 are provided. In some aspects, LAG3 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.

Abstract: Provided herein are methods for treating cancer using molecules having an antigen binding fragment that immunospecifically binds to BTN1A1, such as anti-BTN1A1 antibodies. These molecules include those having an antigen binding fragment that immunospecifically binds to glycosylated BTN1A1, such as anti-glycosylated BTN1A1 antibodies. Also included are molecules having an antigen binding fragment that immunospecifically bind to BTN1A1 dimers, such as anti-BTN1A1 dimer antibodies. Also provided are methods for treating anti-PD-1 therapy or anti-PD-L1 therapy resistant or refractory cancers.

Abstract: Methods for producing and screening for antibodies that specifically bind to glycosylated immune checkpoint proteins (ICPs) relative to non-glycosylated ICPs are provided. Such antibodies recognize specific epitopes of glycosylated ICPs and can prevent or block the binding of a glycosylated ICP with its ligand, such as another ICP, and can inhibit the interactions between the two proteins that can lead to immunosuppression, as exemplified by the human PD-L1/PD-1 interaction. By way of specific example, human PD-L1 and PD-1 polypeptides comprising glycosylated amino acid residues within their extracellular domains are provided for generating anti-glycosylated PD-L1 or anti-glycosylated PD-1 antibodies that specifically bind PD-L1 or PD-1, respectively, and inhibit the PD-L1/PD-1 interaction. The antibodies produced and selected by the methods are especially useful as cancer therapeutics for disrupting, blocking, or neutralizing the ICP system and specific ICP interactions therein.

Abstract: Provided herein are molecules having an antigen binding fragment that immunospecifically binds to BTN1A1, such as anti-BTN1A1 antibodies. These molecules include those having an antigen binding fragment that immunospecifically binds to glycosylated BTN1A1, such as anti-glycosylated BTN1A1 antibodies. Methods of making and using these molecules are also provided, including methods of using them in cancer therapies, or as cancer diagnostics.

Abstract: Provided herein are methods for treating cancer using molecules having an antigen binding fragment that immunospecifically binds to BTN1A1 or a BTN1A1 ligand, such as anti-BTN1A1 antibodies or anti-BTN1A1 ligand antibodies. Also provided herein are BTN1A1 ligands, such as Galectin-1, Galectin-9, Neuropilin-2, and B- and T-Lymphocyte Attenuator.

Abstract: Provided herein are molecules having an antigen binding fragment that immunospecifically binds to BTN1A1, such as anti-BTN1A1 antibodies. These molecules include those having an antigen binding fragment that immunospecifically binds to glycosylated BTN1A1, such as anti-glycosylated BTN1A1 antibodies. Methods of making and using these molecules are also provided, including methods of using them in cancer therapies, or as cancer diagnostics.