A DNA composition useful for eliciting an immune response against tumor-associatedmacrophages comprises a DNA construct that encodes for a cysteine endopeptidase(e.g., legumain) or a polypeptide comprising at least one immunogenic fragmentthereof that is overexpressed in tumor-associated cells such as tumor-associatedmacrophages, or an immunogenic fragment thereof that is expressible in immunecells, and which is incorporated in a pharmaceutically acceptable carrier.In preferred embodiments, the composition encodes a polypeptide comprisinga plurality of immunogenic fragments of a tumor associated cysteine endopeptidase(e.g., legumain) joined together serially such that each fragment is connectedto at least one other fragment by a linker peptide such as AIaAIaAIa or AlaAlaTyr.In one preferred embodiment, the composition also includes a DNA construct thatencodes an immune effector protein, such as a cytokine. The DNA composition ofthe invention can be used alone or in combination with a chemotherapeutic agentto treat diseases such as tumors and tumor metastases.
