This study investigates the enhancement of CD3 bispecific antibody (CD3 bsAb) therapy in solid tumors by pre-treatment with vaccines. CD3 bsAb therapy has shown clinical efficacy in hematological malignancies but has limited success in solid tumors due to insufficient T-cell infiltration. The researchers found that pre-treatment with tumor-unrelated vaccines, such as synthetic long peptides and viruses, can induce CXCR3-mediated T-cell influx into immunologically 'cold' tumors in male mice. This infiltration, when combined with CD3 bsAb administration, leads to the activation and infiltration of effector CD8 T cells into the tumor cell nests, creating a broadly inflamed Th1-type tumor microenvironment. This combination therapy effectively eradicates tumors. The study also demonstrates that multiple vaccination formulations can enhance the efficacy of CD3 bsAb therapy, suggesting that eliciting tumor-(un)related T-cell infiltration can significantly improve the treatment of solid tumors.This study investigates the enhancement of CD3 bispecific antibody (CD3 bsAb) therapy in solid tumors by pre-treatment with vaccines. CD3 bsAb therapy has shown clinical efficacy in hematological malignancies but has limited success in solid tumors due to insufficient T-cell infiltration. The researchers found that pre-treatment with tumor-unrelated vaccines, such as synthetic long peptides and viruses, can induce CXCR3-mediated T-cell influx into immunologically 'cold' tumors in male mice. This infiltration, when combined with CD3 bsAb administration, leads to the activation and infiltration of effector CD8 T cells into the tumor cell nests, creating a broadly inflamed Th1-type tumor microenvironment. This combination therapy effectively eradicates tumors. The study also demonstrates that multiple vaccination formulations can enhance the efficacy of CD3 bsAb therapy, suggesting that eliciting tumor-(un)related T-cell infiltration can significantly improve the treatment of solid tumors.