Provided herein are compositions and methods for eliciting an immune response in a subject. In particular, the present disclosure is directed to fusion proteins comprising an epidermal growth factor receptor variant III (EGFRvIII) polypeptide and a mesothelin polypeptide, and methods of eliciting an immune response using host cells comprising nucleic acid molecules encoding said fusion proteins. In some embodiments, the nucleic acid molecules can encode an EGFRvIII-mesothelin fusion protein comprising an amino acid sequence that is at least i) 90% identical, ii) 95% identical, or iii) 99% identical to EGFRvIIIx5-mesothelin35-622 as set forth in SEQ ID NO:8.
