Abstract: he disclosure relates to the engineering of collagen-binding modification of masked therapeutic agents comprising one or more tumor-associated protease cleavage sites. Upon exposure to tumor-associated proteases in the tumor microenvironment, the polypeptide is cleaved, which unmasks the therapeutic agent, reducing off-target side effects and toxicity associated with systemic administration. Accordingly, aspects of the disclosure relate to a polypeptide comprising a therapeutic agent linked to a masking agent through a linker, wherein the linker comprises one or more tumor-associated protease cleavage sites, and wherein the masking agent blocks the association of the therapeutic agent to its therapeutic target, and further wherein the polypeptide is operatively linked to a collagen binding domain or a tumor-targeting agent.

Abstract: The disclosure relates to the engineering of collagen-binding modification of anti-inflammatory agents using collagen-binding peptide (CBP) and vWF A3 to achieve targeted therapy for inflammatory diseases. Accordingly, embodiments of the disclosure relate to a composition comprising an anti-inflammatory agent operatively linked to an extracellular matrix (ECM)-affinity peptide. Also disclosed are cytokines and anti-inflammatory agents, such as CD200, linked to a serum protein and/or an ECM-affinity peptide. Further aspects of the disclosure relate to a method for treating an autoimmune or inflammatory condition in a subject comprising administering a composition of the disclosure to the subject.

Abstract: The methods and compositions described herein address the need in the art by providing compositions and methods for a therapy with a cytokine that is specifically targeted to and/or retained intra- or peri-tumorally, limiting systemic exposure and reducing side-effects. Accordingly, aspects of the disclosure relate to a composition comprising an immunotherapeutic antibody operatively linked to an extracellular matrix (ECM)-affinity peptide. An ECM-affinity peptide is one that has affinity for an extracellular matrix protein.