Tumor-targeted agonistic CD28 antigen binding molecules

A polynucleotide or set of polynucleotides encoding a bispecific agonistic CD28 antigen binding molecule characterized by monovalent binding to CD28, wherein said bispecific agonistic CD28 antigen binding molecule comprises

• (a) one antigen binding domain capable of specific binding to CD28, wherein the antigen binding domain capable of specific binding to CD28 comprises a heavy chain variable region (VHCD28) comprising a CDR-H1 of SEQ ID NO:
• 489, a CDR-H2 of SEQ ID NO:
• 490, and a CDR-H3 of SEQ ID NO:38 (SHYGX5DX6NFDV) wherein X5 is L and X6 is F, and a light chain variable region (VLCD28) comprising a CDR-L1 of SEQ ID NO:
• 492, a CDR-L2 of SEQ ID NO:
• 493 and a CDR-L3 of SEQ ID NO:
• 494;
• (b) at least one antigen binding domain capable of specific binding to a tumor-associated antigen, and
• (c) an Fc domain composed of a first and a second subunit capable of stable association comprising one or more amino acid substitution that reduces the binding affinity of the antigen binding molecule to an Fc receptor and/or effector function compared to a native IgG1 Fc domain.