ERBB2 and neoplasm: Based on the construction of HCT-mono-mIL12 variants with distinct anti-HER2 binding kinetics, we here provide the first in vivo evidence that tumor antigen binding kinetics and affinity play critical roles in tumor retention and intratumoral diffusion of the immunocytokine, thereby determining the tumor infiltration and intratumoral distribution of antitumor effector T cells and consequently their antitumor efficacy in immunocompetent TBM models.