Provided is a bispecific recombinant protein, comprising a high affinity tumor-targeting arm and a low affinity fusion protein blocking the interaction of CD47 with SIRPα. The antibody corresponding to the high affinity tumor-targeting arm does not bind to CD47, and its binding affinity to the target antigen on the tumor cell is at least 6 times as great as the binding affinity of monomer fusion protein homodimer corresponding to the low affinity fusion protein blocking the interaction of CD47 with SIRPα, to a CD47 on the tumor cell, wherein the low affinity fusion protein blocking the interaction of CD47 with SIRPα comprises a SIRPα extracellular truncation. Also provided are nucleic acid molecules encoding recombinant proteins and the use of the recombinant proteins and nucleic acid molecules in the manufacture of a medicament for treating tumors.

Provided herein are multi-chain chimeric polypeptides that include: (a) a first chimeric polypeptide including a first target-binding domain, a soluble tissue factor domain, and a first domain of a pair of affinity domains; and (b) a second chimeric polypeptide including a second domain of a pair of affinity domains and a second target-binding domain, where the first chimeric polypeptide and the second chimeric polypeptide associate through the binding of the first domain and the second domain of the pair of affinity domains. Also provided here are methods of using these multi-chain chimeric polypeptides and nucleic acids encoding these multi-chain chimeric polypeptides.

This document relates to methods and materials for targeted expansion of immune effector (Eff) T cells. For example, a composition containing one or more amino acid chains (e.g., one or more single-chain antibody/cytokine fusion proteins (immunocytokines)) that can bind to a heterodimeric receptor including an interleukin-2 receptor-β (IL-2Rβ) polypeptide and a common gamma chain (γ.sub.c) polypeptide (e.g., an IL-2Rβ/γ.sub.c polypeptide complex) can be administered to a mammal to stimulate Effs within the mammal to activate an immune response in that mammal. In some cases, methods and materials that can be used to treat a mammal having a condition that can benefit from activating an immune response (e.g., a cancer and/or an infectious disease) are provided. For example, a composition containing one or more single-chain immunocytokines that can bind to an IL-2Rβ/γ.sub.c polypeptide complex can be administered to a mammal having a cancer and/or an infectious disease to treat the mammal.

Fusion polypeptides including at least one Fc binding domain linked to at least one integrin binding domain are provided. In some embodiments, the at least one Fc binding domain is one or more Fc binding domains from Protein A, Protein G, or Protein Z and the at least one integrin binding domain comprises one or more fibronectin type III domains (for example repeats 12-14 of fibronectin type III domains and optionally the connecting segment of fibronectin). Protein complexes including the polypeptide and one or more antibodies are also provided. Methods of using the polypeptide and/or polypeptide:antibody complex are provided, including treating a subject with a tumor, inducing an immune response to a tumor, and/or targeting an antibody to a tumor cell.

The present disclosure provides T-cell modulatory multimeric polypeptides (T-Cell-MMP) and their epitope conjugates comprising at least one immunomodulatory polypeptide (“MOD”) that may be selected to exhibit reduced binding affinity to a cognate co-immunomodulatory polypeptide (“Co-MOD”). The epitope may be, for example, a cancer-associated epitope, an infectious disease-associated epitope, or a self-epitope. The T-Cell-MMP-epitope conjugates are useful for modulating the activity of a T-cell by delivering immunomodulatory peptides, such as IL-2 or IL-2 variants that exhibit reduced binding affinity for the IL-2R, to T-cells in an epitope selective/specific manner, and accordingly, for treating individuals with a cancer, infectious disease or autoimmune disorder.

Modified macrophage immune cells are provided for treatment of cancer and other diseases. In particular said macrophages express chimeric antigen receptors (CAR). The single chain variable fragment (scFv) may be directed against thymidine kinase 1 (TK1) or hypoxanthine guanine phosphoribosyltransferase (HPRT). The signaling domain may be derived from a Toll-like receptor (TLR).

The present invention relates to engineered extra-cellular vesicle internalizing receptors that have the ability to enhance uptake, processing, and presentation to T-cells of tumor-associated antigens by an antigen-presenting cell. It further relates to vectors or antigen presenting cells expressing said receptors, composition and uses thereof for the prevention and/or treatment of a cancer.

The invention relates to a polypeptide comprising a C3 convertase effector domain, a C5 convertase effector domain and optionally a terminal complex inhibitory effector domain which is resistant to deregulation by physiologic FHR-Proteins and has a dimerization motif, and to its therapeutic use.

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.

Provided herein are antibodies to DC-SIGN, conjugates of DC-SiGN antibodies, and DC-SiGN antibody fusion proteins and the use of such antibodies, conjugates, and fusion proteins for the treatment of diseases such as cancer.