In other studies, the antitumor efficacy of bispecific antibody constructs cross-linking HER2 or CD33 with CD3 could also be improved by blocking PD-L1, which is expressed on tumor cells and inhibits T-cell responses via ligation of PD-1 [32, 33]. In contrast to these constructs, trAbs have a unique Fc region comprising the mouse IgG2a and the rat IgG2b isotype, which enables the preferential interaction with activating Fc receptors . Thus, trAbs not only mediate direct cell lysis but also induce a long-lasting T cell-dependent immunologic antitumor memory, because accessory cells expressing activating Fc receptors are stimulated and present tumor-derived peptides to the immune system [13, 15–17]. The vaccination effect exerted by trAbs involves a polyvalent T-cell response, which is directed against numerous TAAs and does not depend on the antigen targeted by the therapeutic trAb [16, 17]. This was shown by challenging mice with the parental melanoma cell line B16F0, which did not express the antigens recognized by the trAb used for vaccination. Polyvalent immune responses are thought to be superior to immunity against single TAAs because tumor immune escape due to antigen loss becomes less likely [34, 35].