DNA COMPOSITION FOR ELICITING AN IMMUNE RESPONSE AGAINST TUMOR-ASSOCIATED MACROPHAGES

摘要

A DNA composition useful for eliciting an immune response against tumor-associated macrophages comprises a DNA construct that encodes for a cysteine endopeptidase (e.g., legumain) or a polypeptide comprising at least one immunogenic fragment thereof that is overexpressed in tumor-associated cells such as tumor-associated macrophages, or an immunogenic fragment thereof that is expressible in immune cells, and which is incorporated in a pharmaceutically acceptable carrier. In preferred embodiments, the composition encodes a polypeptide comprising a plurality of immunogenic fragments of a tumor associated cysteine endopeptidase (e.g., legumain) joined together serially such that each fragment is connected to 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 that encodes an immune effector protein, such as a cytokine. The DNA composition of the invention can be used alone or in combination with a chemotherapeutic agent to treat diseases such as tumors and tumor metastases.