The disclosure relates to binding molecules that bind specifically to prostate specific membrane antigen (PSMA), in particular, single human variable heavy chain domain antibodies and related methods for treatment of cancer.

The invention relates to compositions and methods of constructs comprising a SIRP-? polypeptide, including SIRP-? variants. The constructs may be engineered in a variety of ways to respond to environmental factors, such as pH, hypoxia, and/or the presence of tumor-associated enzymes or tumor-associated antigens. The constructs of the invention may be used to treat various diseases, such as cancer, preferably solid tumor or hematological cancer.

This disclosure provides antibody-urease conjugates having therapeutic utility. More specifically, the disclosure relates to therapeutic conjugates that are prepared by conjugating one or more antibodies to urease, and their use in the diagnosis and treatment of disease.

A poly ADP-ribose polymerase (PARP)-antibody conjugate including an automodified PARP having a plurality of poly ADP-ribose (ADPr) polymers, wherein the poly ADPr polymers comprise a plurality of 3-azido ADP-ribose moieties; and one or more antibody molecules conjugated to one or more of the plurality of 3-azido ADP-ribose moieties, wherein the one or more antibody molecules specifically bind to both a cancer cell surface marker protein and an immune cell surface marker protein, and wherein at least one of the plurality of 3-azido ADP-ribose moieties is not conjugated to the antibody molecules.

Provided herein are compositions, methods, kits and systems for treating cells, tissues and subjects to alter age-related biology (e.g., to study or to treat age-related diseases and conditions). In particular, provided herein are compositions, methods, and uses for inhibition or modification of sialic acid or its cognate receptor to restore phagocytosis in aged cells.

The present disclosure relates to methods for treatment of mucopolysaccharidosis type I in a subject in need thereof by administering a pharmaceutical composition containing a fusion protein of an anti-human transferrin receptor antibody and human ?-L-iduronidase.

The present disclosure relates to identifying novel tumor immune evasion targets. A CRISPR activation screen was employed to identify novel checkpoint inhibitor targets, where upon upregulation, conferred tumor resistance to cytotoxic T cells in model cancer cell lines. Using MAGeCK and FDR analyses to identify candidate genes that were enriched in cancer cells, B3GNT2, MCL1, BCL2A1 and JUNB were identified as the most enriched after a pathway analysis of the top 576 genes prioritized by MAGeCK. Currently, these four genes have not been identified or suggested as possible checkpoint inhibitor targets. Provided herein are methods of targeting the expression or activity of B3GNT2, MCL1, BCL2A1 and JUNB using small molecule agents and/or gene editing methods with the aim of enhancing anti-tumor immunity in subjects in need thereof.

The present invention relates to conjugates, in particular antibody-drug conjugates and immunotoxins, having the formula I: A-(L-D)p (I) or a pharmaceutically acceptable salts or solvates thereof, wherein: A is an antibody that selectively binds FAP; L is a linker; D is a drug comprising a cytolysin or a Nigrin-b A-chain; and p is 1 to 10, and to use of such conjugates in the therapeutic treatment of tumors. Methods of producing such conjugates and components for use in such methods are disclosed.

Aspects of the disclosure relate to methods and compositions useful for in vivo and/or in vitro enzyme profiling. In some embodiments, the disclosure provides methods of in vivo enzymatic processing of exogenous molecules followed by detection of signature molecules as representative of the presence of active enzymes associated with diseases or conditions. In some embodiments, the disclosure provides compositions and in vitro methods for localization of enzymatic activity in a tissue sample.

Provided are conjugates of an arginine deiminase (ADI) and a Tumor Necrosis Factor (TNF) superfamily ligand, and related compositions and methods of use thereof. Also provided are conjugates of a hexameric polypeptide and a trimeric polypeptide, conjugates of a first and second trimeric polypeptide, and related compositions and methods of use thereof.