Antibody-IL2 engrafted proteins and methods of use in the treatment of cancer

An antibody cytokine engrafted protein comprising:

• (a) an IgG class heavy chain comprising an IgG class heavy chain variable region (VH), comprising Complementarity Determining Regions (CDR) HCDR1 comprising SEQ ID NO:
• 7, SEQ ID NO:
• 10, SEQ ID NO:
• 13, SEQ ID NO:
• 16, SEQ ID NO:
• 39, SEQ ID NO:
• 42, SEQ ID NO:
• 45, or SEQ ID NO:
• 48, HCDR2 comprising SEQ ID NO:
• 8, SEQ ID NO:
• 11, SEQ ID NO:
• 14, SEQ ID NO:
• 17, SEQ ID NO:
• 40, SEQ ID NO:
• 46 or SEQ ID NO:
• 49, and HCDR3 comprising SEQ ID NO:
• 9, SEQ ID NO:
• 12, SEQ ID NO:
• 15, SEQ ID NO:
• 18, SEQ ID NO:
• 41, SEQ ID NO:
• 44, SEQ ID NO:
• 47 or SEQ ID NO:
• 50, and wherein the HCDRs individually comprise between 0 to 1 substitution;
• and
• (b) an IgG class light chain comprising an IgG class light chain variable region (VL), comprising LCDR1 comprising SEQ ID NO:
• 23, SEQ ID NO:
• 26, SEQ ID NO:
• 29, SEQ ID NO:
• 32, SEQ ID NO:
• 55, SEQ ID NO:
• 58, SEQ ID NO:
• 61 or SEQ ID NO:
• 64, LCDR2 comprising SEQ ID NO:
• SEQ ID NO:
• 24, SEQ ID NO:
• 27, SEQ ID NO:
• 30, SEQ ID NO:
• 33, SEQ ID NO:
• 56, SEQ ID NO:
• 59, SEQ ID NO:
• 62 or SEQ ID NO:
• 65, and LCDR3 comprising SEQ ID NO:
• 25, SEQ ID NO:
• 28, SEQ ID NO:
• 31, SEQ ID NO:
• 34, SEQ ID NO:
• 57, SEQ ID NO:
• 60, SEQ ID NO:
• 63 or SEQ ID NO:
• 66, and wherein the LCDRs individually comprise between 0 to 1 substitution, and
• a mutated Interleukin 2 (IL2) molecule engrafted into HCDR1, wherein the HCDR1 comprises SEQ ID NO:
• 7, SEQ ID NO:
• 10, SEQ ID NO:
• 13, SEQ ID NO:
• 16, SEQ ID NO:
• 39, SEQ ID NO:
• 42, SEQ ID NO:
• 45, or SEQ ID NO:
• 48, wherein the antibody cytokine engrafted protein preferentially expands T effector cells over regulatory T cells.

An antibody cytokine engrafted protein comprising:

• (a) an IgG class heavy chain comprising an IgG class heavy chain variable region (VH), comprising Complementarity Determining Regions (CDR) HCDR1 comprising SEQ ID NO:
• 7, SEQ ID NO:
• 10, SEQ ID NO:
• 13, SEQ ID NO:
• 16, SEQ ID NO:
• 39, SEQ ID NO:
• 42, SEQ ID NO:
• 45, or SEQ ID NO:
• 48, HCDR2 comprising SEQ ID NO:
• 8, SEQ ID NO:
• 11, SEQ ID NO:
• 14, SEQ ID NO:
• 17, SEQ ID NO:
• 40, SEQ ID NO:
• 46 or SEQ ID NO:
• 49, and HCDR3 comprising SEQ ID NO:
• 9, SEQ ID NO:
• 12, SEQ ID NO:
• 15, SEQ ID NO:
• 18, SEQ ID NO:
• 41, SEQ ID NO:
• 44, SEQ ID NO:
• 47 or SEQ ID NO:
• 50, and wherein the HCDRs individually comprise between 0 to 1 substitution;
• and
• (b) an IgG class light chain comprising an IgG class light chain variable region (VL), comprising LCDR1 comprising SEQ ID NO:
• 23, SEQ ID NO:
• 26, SEQ ID NO:
• 29, SEQ ID NO:
• 32, SEQ ID NO:
• 55, SEQ ID NO:
• 58, SEQ ID NO:
• 61 or SEQ ID NO:
• 64, LCDR2 comprising SEQ ID NO:
• SEQ ID NO:
• 24, SEQ ID NO:
• 27, SEQ ID NO:
• 30, SEQ ID NO:
• 33, SEQ ID NO:
• 56, SEQ ID NO:
• 59, SEQ ID NO:
• 62 or SEQ ID NO:
• 65, and LCDR3 comprising SEQ ID NO:
• 25, SEQ ID NO:
• 28, SEQ ID NO:
• 31, SEQ ID NO:
• 34, SEQ ID NO:
• 57, SEQ ID NO:
• 60, SEQ ID NO:
• 63 or SEQ ID NO:
• 66, and wherein the LCDRs individually comprise between 0 to 1 substitution;
• and
• (c) a mutated Interleukin 2 (IL2) molecule engrafted into HCDR1, wherein the HCDR1 comprises SEQ ID NO:
• 7, SEQ ID NO:
• 10, SEQ ID NO:
• 13, SEQ ID NO:
• 16, SEQ ID NO:
• 39, SEQ ID NO:
• 42, SEQ ID NO:
• 45, or SEQ ID NO:
• 48;
• wherein the antibody cytokine engrafted protein stimulates one or more of CD8+ T effector cell proliferation, natural killer (NK) cell proliferation or combination thereof, greater than recombinant IL2 or aldesleukin.