GM‐CSF and IL‐7 fusion cytokine engineered tumor vaccine generates long‐term Th‐17 memory cells and increases overall survival in aged syngeneic mouse models of glioblastoma

Abstract

AbstractAge‐related immune dysfunctions, such as decreased T‐cell output, are closely related to pathologies like cancers and lack of vaccine efficacy among the elderly. Engineered fusokine, GIFT‐7, a fusion of interleukin 7 (IL‐7) and GM‐CSF, can reverse aging‐related lymphoid organ atrophy. We generated a GIFT‐7 fusokine tumor vaccine and employed it in aged syngeneic mouse models of glioblastoma and found that peripheral vaccination with GIFT‐7TVax resulted in thymic regeneration and generated durable long‐term antitumor immunity specifically in aged mice. Global cytokine analysis showed increased pro‐inflammatory cytokines including IL‐1β in the vaccinated group that resulted in hyperactivation of dendritic cells. In addition, GIFT‐7 vaccination resulted in increased T‐cell trafficking to the brain and robust Th‐17 long‐term effector memory T‐cell formation. TCR‐seq analysis showed increased productive frequency among detected rearrangements within the vaccinated group. Overall, our data demonstrate that aging immune system can be therapeutically augmented to generate lasting antitumor immunity.