Novel multispecific constructs have already incorporated some essential synergistic effects, for example, “checkpoint-inhibitory T-cell engagers” (CiTEs) are BiTEs equipped with an additional moiety blocking the PD-1/PD-L1 axis or another immune checkpoint [230], while “simultaneous multiple interaction T-cell engagers” (SMITEs) are the combined administration of different BiTEs in order to target multiple TAAs and/or turn tumor-cell inhibitory (e.g., from PD-L1) into T-cell costimulatory (e.g., via CD28) signals [231,232]. Here, CD28 is linked to neoplasm.