Abstract: This disclosure relates to linker polypeptides. In some embodiments, the linker polypeptide comprises a first targeting sequence; a second targeting sequence; and a first linker between the first targeting sequence and the second targeting sequence, the linker comprising a protease-cleavable polypeptide sequence. In some embodiments, the linker polypeptide comprises a first active domain; a second active domain; a pharmacokinetic modulator; and a first linker between the pharmacokinetic modulator and the first active domain, the first linker comprising a protease-cleavable polypeptide sequence. In some embodiments, the linker polypeptide comprises a first active domain; an inhibitory polypeptide sequence capable of blocking an activity of the first active domain; a first linker between the first active domain and the inhibitory polypeptide sequence, the linker comprising a protease-cleavable polypeptide sequence; and a first targeting sequence.

Abstract: This disclosure relates to protease-cleavable cytokine prodrugs. In some embodiments, the prodrugs comprise a targeting sequence. In some embodiments, the prodrugs comprise a pharmacokinetic modulator.

Abstract: Provided herein are methods for activating an immune cell in a subject. In some embodiments, the methods comprise passing an immune cell from a subject through an immune modulating chamber comprising a tumor cell, thereby activating the immune cell, and returning the activated immune cell to the subject. In some embodiments, the methods further comprise isolating an immune cell-containing portion of a sample and passing the immune cell-containing portion through the immune modulating chamber. Methods of treating cancer and methods of inducing an immune response against a tumor are also provided herein.