Provided herein are antibodies comprising multiple non-natural amino acid residues at site-specific positions, compositions comprising the antibodies, methods of their production and methods of their use. The antibodies are useful for methods of treatment and prevention, methods of detection and methods of diagnosis.

A long acting modified T-cell engager bispecific antibody with cytokine caps that provides reduced toxicity and boosted anti-tumor activity is disclosed. Method of making the modified and cytokine capped Bi-specific T-cell engager antibody is also disclosed.

Provided are a monoclonal antibody-cytokine fusion protein dimer and an application thereof. The monoclonal antibody comprises two heavy chains, the fusion protein dimer comprises a first heavy chain polypeptide chain and a second heavy chain polypeptide chain, wherein one heavy chain of the monoclonal antibody is connected to a cytokine to form the first heavy chain polypeptide chain, and the other heavy chain of the monoclonal antibody is optionally connected to another cytokine to form the second heavy chain polypeptide chain. The monoclonal antibody-cytokine fusion protein dimer provided not only fully retains the biological activity of the antibody, but also significantly improves the biological activity of the cytokine(s). More importantly, by using the target specificity of the antibody molecule, the immune response of immune cells is enhanced and the toxicity of the cytokine(s) is reduced, and thus, on the premise of enhancing the efficacy of the drug, the safety of the medication is ensured.

The present invention relates, in part, to targeted chimeric proteins with beneficial therapeutic effects, including, for example, effects mediated by chimeric proteins which comprise modified signaling agents two or more targeting moieties. Methods of treatment and pharmaceutical compositions comprising the chimeric proteins are also provided. The present invention finds use in the treatment of various disease and disorders.

Provided are activatable proproteins comprising at least two separate polypeptide chains, the first comprising IL-2 fused to a masking moiety and the second comprising an IL-2 binding protein fused to a masking moiety, and related pharmaceutical compositions and methods of use thereof.

Provided is a complex composition, of which positional isomers are minimized by using a N-terminus of an immunoglobulin Fc region as a binding site when the immunoglobulin Fc region is used as a carrier. Also provided are a protein complex which is prepared by N-terminal-specific binding of immunoglobulin Fc region, thereby prolonging blood half-life of the physiologically active polypeptide, maintaining in vivo potency at a high level, and having no risk of immune responses, a preparation method thereof, and a pharmaceutical composition including the same for improving in vivo duration and stability of the physiologically active polypeptide. The protein complex may be usefully applied to the development of long-acting formulations of various physiologically active polypeptide drugs.

The present application relates to conjugates comprising interleukin 2 (IL2), and a mutant of tumour necrosis factor, such as tumour necrosis factor alpha (TNFα), and an antibody molecule. The antibody molecule preferably binds to an antigen associated with neoplastic growth and/or angiogenesis, such as the Extra-Domain A (EDA) or Extra-Domain B (EDB) of fibronectin. The conjugate may be used in the treatment of cancer.

The present invention is directed to compositions of matter useful for the diagnosis and treatment of tumor in mammals and to methods of using those compositions of matter for the same.

The present invention relates to an immunocytokine comprising (a) a conjugate, and (b) an immunomodulatory antibody or a fragment thereof directly or indirectly linked by covalence to said conjugate, wherein said conjugate comprises (i) a polypeptide comprising the amino acid sequence of the interleukin 15 or derivatives thereof, and a polypeptide comprising the amino acid sequence of the sushi domain of the IL-15Rα or derivatives thereof; and uses thereof.

To allow control over injected genetically engineered cells, it is helpful that the genetically engineered cells express a marker that can be used to detect such cells among a pool of unmodified cells. Some embodiments relate to a marked protein comprising a TCR constant domain and an exogenous amino acid variation that comprises a sequence that is detectable and identifiable within the TCR constant domain. Other embodiments relate to an antibody epitope that is attached to a TCR chain. Both the marked proteins and the antibody epitopes can be used to track genetically engineered cells.