The present disclosure provides a use of a dimer in the preparation of a medicament for treating a tumor in a subject in need thereof, and the dimer formed by two polypeptide chains, with each of the two polypeptide chains comprising an antibody Fc subunit, wherein the dimer comprises two or more immunoglobulin single variable domains (ISVDs), at least one of the ISVDs is specific for PD-L1, and at least one of the ISVDs is specific for CTLA4. The present disclosure also provides a method for treating a tumor in a subject in need thereof, wherein the subject is resistant to the therapy of an immune checkpoint inhibitor.

A method for improving the solubility of a physiologically active protein or peptide compared to that of a physiologically active protein or peptide which is not conjugated to an immunoglobulin Fc fragment is disclosed. The method includes steps of conjugating the physiologically active protein or peptide to an immunoglobulin Fc fragment. Also disclosed is a composition for improving the solubility of a physiologically active protein or peptide, which contains an immunoglobulin Fc fragment. The composition improves the solubility compared to a composition without an immunoglobulin Fc fragment.

The present invention relates to multimers of polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. The invention also describes the multimerization of polypeptides through various chemical linkers and hinges of various lengths and rigidity using different sites of attachments within polypeptides. In particular, the invention describes multimers of peptides which are high affinity binders and activators of CD137. The invention also includes drug conjugates comprising said peptides, conjugated to one or more effector and/or functional groups, to pharmaceutical compositions comprising said peptide ligands and drug conjugates and to the use of said peptide ligands and drug conjugates in preventing, suppressing or treating a disease or disorder mediated by CD137.

The present invention relates, inter alia, to compositions and methods, including heterodimeric proteins that find use in the treatment of disease, such as immunotherapies for cancer and autoimmunity.

Disclosed herein include methods, compositions, and kits suitable for use in detecting the activation level of a signal transducer. In some embodiments, there are provided synthetic protein circuits wherein recruitment of synthetic protein circuit components to an association location upon activation of a signal transducer generates an active effector protein. The effector protein can be configured to carry out a variety of functions when in an active state, such as, for example, inducing cell death. Methods of treating a disease or disorder characterized by aberrant signaling are provided in some embodiments.

Provided herein are modified T cell engagers, pharmaceutical compositions thereof, as well as nucleic acids, and methods for making and discovering the same. The modified T cell engagers described herein are modified with a peptide and a half-life extending molecule.

The invention provides highly effective and versatile CRISPR/Cas protein variants, compositions, methods and uses thereof in gene editing. More specifically, the invention relates to PAM-reduced or PAM-abolished Cas proteins and chimeras, complexes and conjugates thereof, genetic editing systems and to therapeutic and non-therapeutic methods and uses of the PAM-reduced or PAM-abolished Cas proteins.

Provided is a polypeptide tag. The amino acid sequence of the polypeptide tag is Xaa1Xaa2Xaa3PHDYNXaa4Xaa5Xaa6 (SEQ ID NO: 37), wherein in the formula, Xaa1, Xaa2, Xaa3, Xaa4, Xaa5, and Xaa6 are each independently an amino acid or none. The polypeptide tag is used for labeling a target protein. In a second aspect, provided is a polypeptide fusion protein, comprising the following two structures: (1) any polypeptide tag according to the first aspect, and (2) a target protein connected to the polypeptide tag. Also provided are an in vitro cell-free protein synthesis system and an application thereof in in vitro protein synthesis. By constructing the polypeptide tag and a target protein as a fusion protein, the expression of the labeled target protein can be effectively increased without removing the polypeptide tag.

Compositions and methods relating to DNase fusion polypeptides are disclosed. The fusion polypeptides include a biologically active DNase joined to the amino-terminus of an immunoglobulin Fc region via a flexible polypeptide linker (e.g., a linker containing at least 26 amino acid residues). Typically, the DNase is a hyperactive and/or actin-resistant DNase1 variant (e.g., a variant of human DNase1 having one or more amino acid substitutions selected from substitutions at Asp-53, Tyr-65, Glu-69, Arg-74, Gly-105, and Ala-114 according to amino acid position numbering of mature wild-type human DNase1) or a DNase1L3 variant (e.g., a variant of human DNase1L3 in which the native nuclear localization signals are removed). In some embodiments, the fusion polypeptide includes a polypeptide segment located carboxyl-terminal to the Fc region and which may be, e.g., a biologically active paraoxonase. Also disclosed are dimeric proteins comprising first and second DNase fusion polypeptides as disclosed herein. The fusion polypeptides and dimeric proteins are useful in methods for therapy, including methods for treating diseases and disorders characterized by NETosis.

Provided are an anti-ST2 antibody or a fragment thereof. The antibody or the fragment thereof can be specifically bound to human ST2, for inhibiting combination of IL-33 and human ST2, blocking an IL-33/ST2 intracellular signaling pathway, and inhibiting the promoting effect of different forms of IL-33 in cell-derived IL5, IL6 and 118 production. Compared with a known anti-ST2 antibody, this anti-ST2 antibody has higher biological activity, and can be used for preventing, treating or alleviating diseases related to ST2 expression or IL-33/ST2 pathway disorders.