An IL12-IL2-Antibody Fusion Protein Targeting Hodgkin%26apos;s Lymphoma Cells Potentiates Activation of NK and T cells for an Anti-Tumor Attack

作者：Jahn Tobias; Zuther Martin; Friedrichs Bjoern; Heuser Claudia; Guhlke Stefan; Abken Hinrich; Hombach Andreas A^*

来源：PLos One, 2012, 7(9): e44482.

DOI：10.1371/journal.pone.0044482

Successful immunotherapy of Hodgkin%26apos;s disease is so far hampered by the striking unresponsiveness of lymphoma infiltrating immune cells. To mobilize both adoptive and innate immune cells for an anti-tumor attack we fused the pro-inflammatory cytokines IL2 and IL12 to an anti-CD30 scFv antibody in a dual cytokine fusion protein to accumulate both cytokines at the malignant CD30(+) Hodgkin/Reed-Sternberg cells in the lymphoma lesion. The tumor-targeted IL12-IL2 fusion protein was superior in activating resting T cells to amplify and secrete pro-inflammatory cytokines compared to targeted IL2 or IL12 alone. NK cells were also activated by the dual cytokine protein to secrete IFN-gamma and to lyse target cells. The tumor-targeted IL12-IL2, when applied by i.v. injection to immune-competent mice with established antigen-positive tumors, accumulated at the tumor site and induced tumor regression. Data demonstrate that simultaneous targeting of two cytokines in a spatial and temporal simultaneous fashion to pre-defined tissues is feasible by a dual-cytokine antibody fusion protein. In the case of IL12 and IL2, this produced superior anti-tumor efficacy implying the strategy to muster a broader immune cell response in the combat against cancer.

• 出版日期2012-9-18