The invention features multi-specific fusion protein complexes with one domain comprising IL-15 or a functional variant and a binding domain specific to IL-12 or IL-18.

The present application provides chimeric antibody-TCR constructs comprising an antigen-binding module that specifically binds to a target antigen and a T cell receptor module capable of recruiting at least one TCR-associated signaling molecule. Also provided are methods of making and using these constructs.

This disclosure relates to methods of treating cancer using multi-specific binding proteins that bind NKG2D, CD16 and a tumor-associated antigen such as HER2. Provided are uses of the multi-specific binding protein in combination with a corticosteroid to reduce the risk of infusion-related reactions. Also provided are uses of the multi-specific binding protein in treating cancer that has low or moderate HER2 expression level. The present disclosure also relates to pharmaceutical formulations comprising the multi-specific binding proteins.

The present invention provides Fc-fused protein constructs, which as monovalent dimers have a higher serum half-life compared to a native/natural molecule, and are, therefore, advantageous for achieving higher titers of the proteins during production, higher stability during storage, and improved efficacy when used as a therapeutic. Also provided are Fc-fused protein constructs having mutations in the Fc region that reduce effector functions, which have increased activity to inhibit tumor growth and are, therefore, advantageous when used as a cancer therapy.

The invention relates to a method for the production of a bispecific CD30×CD16A antibody construct comprising a first binding domain for FcγRIIIa comprising the steps chromatographically capturing the antibody construct from a solution; eluting the antibody construct from the capture matrix; reducing the pH in the solution of the eluted antibody construct to low pH, incubating the antibody construct under these conditions for at least 40 h and neutralizing thereafter.

Fc regions comprising modification to increase the affinity of association between the Fc region and TRIM21 are disclosed. Also disclosed are constituent polypeptides of such Fc regions, antigen-binding molecules and immunogens comprising such Fc regions, and nucleic acids encoding and methods using such Fc regions, antigen-binding molecules and immunogens.

The present invention relates to antibodies or antigen-binding fragments that are useful for treating coronavirus infections (e.g., COVID-19 caused by SARS-CoV-2). The present invention also relates to various pharmaceutical compositions and methods of treating coronavirus using the antibodies or antigen-binding fragments.

Human interleukin-2 (IL-2) muteins or variants thereof are provided. In particular, provided are IL-2 muteins that have an increased binding capacity for IL-2Rβ receptor as compared to wild-type IL-2 for use in combination therapies with anti-PD-1 antibodies for the treatment of cancer. Also provided are pharmaceutical compositions that include such anti-PD-1 antibodies and the disclosed IL-2 muteins.

The present invention relates to a bispecific antibody, which is a tetravalent symmetrical bispecific antibody with a structure of F(ab).sub.2-(Fv).sub.2-Fc and comprises two identical fusion heavy chains and two identical fusion light chains.

The present disclosure provides Fc domain variants, including effector-competent Fc domain variants. The present disclosure also provides nucleic acids encoding Fc domain variants and host cells for making Fc domain variants. Methods for increasing the yield of Fc domain variants, and methods of using Fc domain variants to treat disease, are also provided.