The present disclosure provides methods and compositions that find use in identifying presence of an advanced stage autoimmune liver disease (ALD) is a subject diagnosed as having ALD. Also provided here are methods and compositions that find use in monitoring effectiveness of treatment of an ALD patient receiving a treatment for the ALD. Also provided here are methods and compositions that find use in identifying subjects suffering from a relapse of ALD. The methods and compositions of the present disclosure also find use in facilitating treatment decisions for a subject having ALD. Also provided herein are methods for treating ALD.

The present invention relates to a fusion protein comprising at least two cytokines, of which at least one is a modified cytokine with a strongly reduced binding affinity to its receptor, or to one of its receptors. Preferably, both cytokines are connected by a linker, preferably a GGS linker. The invention relates further to said fusion protein for use in treatment of diseases.

The invention relates to novel Evasin polypeptides with novel chemokine-binding properties and their use in inhibiting chemokines or detecting chemokine expression and inflammation.

The present disclosure relates, in general, to methods for treating cancer comprising administering to a subject in need thereof an effective amount of dendritic cells comprising the human CCL21 gene in combination with an anti-PD-1 antibody. In one aspect, the treatment is amenable to patients with tumors having a high mutational burden.

CNS metastases are a major cause of cancer deaths with few therapeutic options for treatment. Monoclonal anti-body-based therapy is one of the most successful therapeutic strategies for cancer; however, its efficacy is limited against CNS metastases due to insufficient CNS delivery. Here, we show significantly improved antibody delivery to the CNS using novel timed-release nanocapsules that encapsulate individual antibodies within a crosslinked phosphorylcholine polymer and gradually release cargo through hydrolysable crosslinkers. A single course of rituximab (RTX) nanocapsule treatment elevates RTX levels in the CNS by nearly 10-fold compared to native RTX. We improved control of CNS metastases in a murine xenograft model of non-Hodgkin lymphoma; moreover, using a xenograft humanized BLT mouse model, lymphomas were eliminated with a single course of RTX nanocapsule treatment. This approach is useful for treatment of cancers with CNS metastases and is generalizable for delivery of any antibody to the CNS.

Embodiments of the present disclosure pertain to modified antigen presenting cells that include a recombinant protein appended onto a surface of the antigen presenting cells. The recombinant protein can include: an ectodomain positioned on the surface; a transmembrane domain with a region embedded in the cell membrane; an antigen presenting cell recruiting domain that directs the cells towards the cancer cells; and an antigen presenting cell activator that activates or licenses the antigen presenting cells. Additional embodiments of the present disclosure pertain to methods of expressing the recombinant proteins on antigen presenting cells and utilizing the modified antigen presenting cells for treating various cancers in various subjects. Further embodiments of the present disclosure pertain to nucleotide-containing carriers for expressing the recombinant proteins of the present disclosure in antigen presenting cells.

The invention is based on the disclosure provided herein that secondary lymphoid organ chemokine (SLC) inhibits the growth of syngeneic tumors in vivo. Thus, the invention provides a method of treating cancer in a mammal subject by administering a therapeutically effective amount of an SLC to the mammal in combination with a checkpoint inhibitor, including monoclonal antibodies and small molecule inhibitors. Exemplary checkpoint molecules include CTLA-4, a CTLA-4 receptor, PD-1, PD1-L1, PD1-L2, 4-1BB, OX40, LAG-3, TIM-3 or a combination thereof. SLCs useful in the methods of the invention include SLC polypeptides, variants and fragments and related nucleic acids.

This disclosure relates to the field of poly-adenylated (poly-A) tails. In some embodiments, a DNA encodes a poly-A tail located 3′ to nucleotides encoding a protein of interest, wherein the poly-A tail comprises one or more non-adenine nucleotide.

Compositions, methods, and uses of recombinant immunoglobulin proteins, recombinant immunoglobulin protein complexes, carrier protein complexes, and a pharmaceutical composition including one or more of those to increase immune therapy effectiveness are presented. Preferred protein and protein complex comprise one or more functional moieties that includes a binding motif to a tumor-associated antigen, a T-cell activating molecule, and a chemokine. In some embodiments, the pharmaceutical composition includes two or more protein complexes, which are functionally distinct from each other. In other embodiments, the pharmaceutical composition includes a genetically-engineered microorganism including a first tumor-associated antigen and a T-cell activating molecule, a recombinant immunoglobulin protein complex, and a chemokine.

The present invention provides a fusion protein, comprising a chemokine polypeptide, which is a chemokine or a receptor binding domain thereof; and a cytokine polypeptide connected to said chemokine polypeptide, which is an interleukin, a TNF-superfamily cytokine or a receptor-binding domain thereof; wherein the chemokine polypeptide and the cytokine polypeptide have a common target cell, and the fusion protein has an improved chemokine activity as compared to the chemokine polypeptide, and an improved cytokine activity as compared to the cytokine polypeptide.