Evidence for bispecific antibody efficacy against solid tumors is limited, and additional approaches may be required in the clinic to achieve the success seen with hematologic tumors. Chiu et al. address this by designing a CD3 bispecific antibody that also targets a major prostate cancer tumor antigen, prostate-specific membrane antigen (PSMA). Preclinical models show positive responses to bispecific antibody treatment that is dependent on tumor size, with smaller tumors being more sensitive than larger tumors. However, by combining the bispecific antibody with 4-1BB costimulation, larger tumors are more readily reduced due to boosted, durable T-cell responses and the generation of immune memory. The data highlight that tumor size matters and that 4-1BB costimulation can be used to increase the potency of bispecific antibody treatment in solid tumors. Read more in this issue on page 596. Original image from Supplementary Fig. S5A. Artwork by Lewis Long.