Fusion proteins that include an immune (e.g., Treg) targeting moiety and a cytokine or growth factor molecule, pharmaceutical and formulations thereof, and methods of using and making the same, are disclosed.

Provided are ionizable cationic lipids and lipid nanoparticles for the delivery of nucleic acids to cells (e.g., immune cells), and methods of making and using such lipids and targeted lipid nanoparticles.

Provided are an anti-CD11b antibody or an antigen-binding portion thereof, and methods and use of the antibody for modulating immunoresponses by regulating CD11b expression on cells.

The present disclosure provides modified antibodies which contain an antibody or antibody fragment (AB) modified with a masking moiety (MM). Such modified antibodies can be further coupled to a cleavable moiety (CM), resulting in activatable antibodies (AAs), wherein the CM is capable of being cleaved, reduced, photolysed, or otherwise modified. AAs can exhibit an activatable conformation such that the AB is more accessible to a target after, for example, removal of the MM by cleavage, reduction, or photolysis of the CM in the presence of an agent capable of cleaving, reducing, or photolysing the CM. The disclosure further provides methods of making and using such modified antibodies and activatable antibodies.

The present invention, in some aspects, provides methods, reagents, compositions, and kits for the radiolabeling of proteins, for example, of proteins useful for positron emission tomography (PET) or single-photon emission computed tomography (SPECT) (e.g., for diagnostic and therapeutic applications), using sortase-mediated transpeptidation reactions. Some aspects of this invention provide methods for the conjugation of an agent, for example, a radioactive agent or molecule to diagnostic or therapeutic peptides or proteins. Compositions comprising sortagged, radiolabeled proteins as well as reagents for generating radiolabeled proteins are also provided. Kits comprising reagents useful for the generation of radiolabeled proteins are provided, as are precursor proteins that comprise a sortase recognition motif.

Immunostimulatory fusion molecules that include an immune cell targeting moiety and a cytokine molecule, pharmaceutical and formulations thereof, and methods of using and making the same, are disclosed.

Polynucleotides encoding immunostimulatory fusion molecules that include an immune cell targeting moiety and a cytokine molecule, pharmaceutical and formulations thereof, and methods of using and making the same, are disclosed.

The present invention relates to methods for modulating immune response based on binding I-domain of CD11b on the tumor associated myeloid cells (TAMCs) in the tumor microenvironment. Particularly, binding to I-domain of CD11b with anti-CD11b-I-domain antibody triggers immunostimulatory environment that have one or more of the following effects in the tumor microenvironment: increase the inflammatory cytokine in the tumor microenvironment, decrease the population of IDO+ myeloid suppresser cells, up-regulate M1 marker over M2 marker on the tumor associated macrophage, increase M1:M2 tumor associated macrophage ratio, promote differentiation of dendritic cells (DC), nature killer dendritic cells (NKDC), and plasmacytoid dendritic cells (pDC), increase population of 41BB+PD1+ neoantigen specific CD8 T cells. Converting cold (non-inflamed) to hot (inflamed) tumor by binding to I-domain of CD11b with anti-CD11b-I-domain antibody allows enhanced effectiveness of immune response modulator.

This disclosure relates to therapeutic use of integrin-binding antibodies.

Particular aspects show that the signal peptide remains intact on the mature CD18 molecule on ruminant leukocytes rendering these cells susceptible to cytolysis by Lkt. Comparative amino acid sequence analysis of the signal peptide of CD18 of eight ruminants and five non-ruminants revealed that the ruminant CD18 signal peptides contain cleavage-inhibiting glutamine (Q), compared to cleavage-conducive glycine in non-ruminants, at position 5 relative to the cleavage site. Mutagenesis of Q at position 5 of the bovine CD18 signal peptide to G resulted in the abrogation of Lkt-mediated cytolysis of transfectants expressing bovine CD18 carrying the Q(5)G mutation. Provided is novel technology to clone cattle and other ruminants expressing CD18 without the signal peptide on their leukocytes, providing ruminants that are less susceptible to M. haemolytica. Methods for treating conditions and/or diseases associated with M. haemolytica (e.g., pneumonic pasteurellosis), comprising administration of polypeptides comprising CD18 signal peptide sequences are also provided.