The present disclosure relates to polynucleotides encoding tethered interleukin-12 (IL-12) polypeptides comprising an IL-12 polypeptide and a membrane domain. The present disclosure also relates to vectors comprising the polynucleotides； host cells comprising the polynucleotides or vectors, polypeptides encoded by the polynucleotides； compositions comprising the polynucleotides, vectors, host cells, or polypeptides and a delivery agent； and uses thereof, including treatment of cancer.
