The present invention relates to recombinant Gram-negative bacterial strains and the use thereof for delivery of heterologous proteins into eukaryotic cells.

Provided are systems and methods for recombinant proteins in microorganisms engineered to use alternate carbon sources.

Anti-PVRIG and anti-TIGIT antibodies are provided.

Provided herein are de novo binding domain containing polypeptides (DBDpp) that specifically bind a target of interest. Nucleic acids encoding the DBDpp, and vectors and host cells containing the nucleic acids are also provided. Libraries of DBDpp, methods of producing and screening such libraries and the DBDpp identified from such libraries and screens are also encompassed. Methods of making and using the DBDpp are additionally provided. Such uses include, without limitation, affinity purification, and diagnostic and therapeutic applications.

There are disclosed fusion proteins comprising the bacterial protein FhuD2 and one or more copies of a heterologous polypeptide, polynucleotides and expression vectors encoding the fusion proteins and bacterial outer membrane vesicles containing them. Other aspects of the invention regard immunogenic compositions comprising the outer membrane vesicles and their use in the prevention or treatment of tumors.

The present disclosure relates to a method of targeting stems cells, in particular non-apoptotic stem cells, employing a GLA domain, capable of binding surface exposed phosphatidyl serine.

The present disclosure relates to a method of intracellular delivery of a molecule employing a GLA domain to facilitate entry into the cell.

In some embodiments the present disclosure pertains to a method of activating an anti-tumor immune response for the treatment of a cancer. In some embodiments, such a method comprises detecting CD26 expression in a subject in need thereof. In some embodiments, the method comprises administering to the subject a therapeutically effective amount of a composition comprising adenosine deaminase. In some embodiments, the adenosine deaminase stimulates T cell proliferation and activates maturation of macrophages or dendritic cells. In some embodiments, the present disclosure pertains to a method for targeted reduction of adenosine or deoxyadenosine in a tumor microenvironment of a solid tumor.

Extracellular drug conjugates (EDCs) targeting CD38 are useful in the treatment of diseases such as cancer and immune disorders, including asthma.

Presented herein are cyclic peptides that specifically bind to a cell surface molecule, thereby allowing cell/tissue-specific targeting. The cyclic peptides can be attached to an agent, for example, a polypeptide such as an antibody, e.g., a cell-penetrating antibody. Cyclic peptide-containing cell/tissue-specific cell-penetrating antibodies described herein are capable of targeted delivery in a cell type-specific or tissue-specific (i.e., cell/tissue-specific) manner. The cell/tissue-specific cell-penetrating antibodies described herein can be used as an effective anticancer agent for cancer that overexpresses a cell membrane protein that specifically binds to the fused cyclic peptides.