Abstract: Disclosed are polypeptides comprising a diphtheria toxin and a PD1 targeting moiety. Disclosed are polypeptides comprising, from N- to C-terminus, a truncated diphtheria toxin, and two anti-PD-1 scFvs. Disclosed are nucleic acid constructs comprising a nucleic acid sequence encoding any one of the disclosed polypeptides. Disclosed are nucleic acid constructs comprising a nucleic acid sequence encoding a diphtheria toxin linked to a nucleic acid sequence encoding a PD1 targeting moiety. Disclosed are methods of treating a subject in need thereof comprising administering to the subject a composition comprising one or more of the disclosed polypeptides, vectors, or pharmaceutical compositions.