Protein heterodimer and use thereof

A protein heterodimer, comprising a first polypeptide chain and a second polypeptide chain different from said first polypeptide chain, wherein said first polypeptide chain comprises interleukin 12(a) (IL12), and said second polypeptide chain comprises interleukin 12b (IL12b);

• said protein heterodimer further comprises interleukin-2 (IL2), granulocyte macrophage colony stimulating factor (GMCSF), and one or more targeting moieties;
• and
• said IL2 is located in said first polypeptide chain, said GMCSF is located in said first polypeptide chain, and said one or more targeting moieties are each independently located in said first polypeptide chain or in said second polypeptide chain;
• wherein said IL2, said IL12a and said GMCSF are sequentially comprised in said first polypeptide chain from the N-terminal to the C-terminal, and said IL12b and one of said one or more targeting moieties are sequentially comprised in said second polypeptide chain from the N-terminal to the C-terminal;
• or
• wherein one of said one or more targeting moieties, said IL12a, said IL2 and said GMCSF are sequentially comprised in said first polypeptide chain from the N-terminal to the C-terminal, and said IL12b and one of said one or more targeting moieties are sequentially comprised in said second polypeptide chain from the N-terminal to the C-terminal;
• wherein any one of said one or more targeting moieties comprises the amino acid sequence as set forth in any one in the group consisting of:
• SEQ ID NOs:
• 1-3.