Anti-HER2 scFv-CCL19-IL7 recombinant protein inhibited gastric tumor growth in vivo

Abstract

AbstractHER-2 targeted therapies, such as monoclonal antibodies (mAbs) and CAR-T cell therapy have been applied in the treatment of various of cancers. However, the anti-HER2 CAR-T cell therapy are limited by its expensive production procedure and fatal side effects such as cytokine storm or “On target, off tumor”. The application of anti-HER2 mAbs to the soild tumor are also plagued by the patients resistant with different mechanisms. Thus, the recombinant protein technology can be presented as an attractive methods in advantage its less toxic and lower cost. In this study, we produced a HER-2-targeting recombinant protein, which is the fusion of the anti-HER-2 single chain fragment variable domain, CCL19 and IL7 (HCI fusion protein). Our results showed that the recombinant protein can induce the specific lysis effects of immune cells on HER-2-positive gastric tumor cells and can suppress gastric tumor growth in a xenograft model by chemotactic autoimmune cell infiltration into tumor tissues and activated T cells. Taken together, our results revealed that the HCI fusion protein can be applied as a subsequent clinical drug in treating HER-2 positive gastric tumors.