PD-1 targeted IL-15/IL-15RALPHA fc fusion proteins and uses in combination therapies thereof

A PD-1 targeted IL-15/Rα heterodimeric Fc fusion protein comprising:

• a) a first monomer comprising, from N- to C-terminal:
• i) a IL-15 Rα sushi domain protein;
• ii) a first domain linker;
• iii) an IL-15 protein;
• and
• iv) a first variant Fc domain;
• and
• b) a second monomer comprising a heavy chain comprising VH-CH1-hinge-CH2-CH3, wherein said CH2-CH3 is a second variant Fc domain;
• c) a third monomer comprising a light chain comprising VL-CL;
• wherein said VH and VL domains form an antigen binding domain that binds to human PD-1 and does not compete for said human PD-1 with nivolumab and/or pembrolizumab;
• wherein said VH domain has at least 95% amino acid sequence identity with SEQ ID NO:5 and said VL domain has at least 95% amino acid sequence identity with SEQ ID NO:6;
• wherein said first variant Fc domain and said second variant Fc domain are each a variant of a human IgG Fc domain.