Trivalent and trispecific antibody constructs and methods of use thereof

An antibody construct, comprising a binding domain capable of binding CD28, wherein the binding domain comprises a VH sequence comprising a HCDR1 having the sequence SX1GVH (SEQ ID NO:

• 302), a HCDR2 having the sequence VIWX2GGX3TNFNSALMS (SEQ ID NO:
• 306), and a HCDR3 having the sequence DRAX4GX5YX6X7AMDY (SEQ ID NO:
• 312), and a VL sequence comprising a LCDR1 having the sequence RASESVEYYX8TSLMQ (SEQ ID NO:
• 315), a LCDR2 having the sequence AASX9 VX10S (SEQ ID NO:
• 319), and a LCDR3 having the sequence QQSRKVPFT (SEQ ID NO:
• 320), having one or more of the following amino acid substitutions at the positions as identified in the CDR sequences:
• X1:
• Y to A, X2:
• P to A, X3:
• G to S, X4:
• S to Y, X5:
• N to A, X6:
• L to N, X7:
• S to Y, X8:
• G to V, X9:
• N to A, and/or X10:
• E to D.

An antibody construct, comprising a binding domain capable of binding Cldn18.2, wherein the binding domain comprises a VH sequence comprising a HCDR1 having the sequence SNPMI (SEQ ID NO:

• 333), a HCDR2 having the sequence IIDTDGSTYYADWAKG (SEQ ID NO:
• 334), and a HCDR3 having the sequence RLHGSSNGYYDDL (SEQ ID NO:
• 335), and a VL sequence comprising a LCDR1 having the sequence QASQSIYSYLS (SEQ ID NO:
• 336), a LCDR2 having the sequence KASTLAS (SEQ ID NO:
• 337), and a LCDR3 having the sequence QQGYTVTNVDKNT (SEQ ID NO:
• 338).