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

Area of Science:

• Oncology
• Immunotherapy
• Biotechnology

Background:

• HER-2 targeted therapies like monoclonal antibodies (mAbs) and CAR-T cell therapy are used for cancer treatment.
• Existing anti-HER2 CAR-T cell therapy faces challenges including high production costs and severe side effects (cytokine storm, "On target, off tumor").
• Anti-HER2 mAbs show limited efficacy in solid tumors due to resistance mechanisms.

Purpose of the Study:

• To develop a novel recombinant protein for HER-2 targeted cancer therapy.
• To evaluate the efficacy and safety of a HER-2-targeting recombinant protein (HCI fusion protein) in gastric cancer models.

Main Methods:

• Production of a recombinant fusion protein combining an anti-HER-2 single-chain variable fragment (scFv), CCL19, and IL-7 (HCI fusion protein).
• Assessment of the recombinant protein's ability to induce specific lysis of HER-2-positive gastric tumor cells.
• Evaluation of the HCI fusion protein's effect on gastric tumor growth in a xenograft model.

Main Results:

• The HCI fusion protein demonstrated specific immune cell-mediated lysis of HER-2-positive gastric tumor cells.
• The recombinant protein suppressed gastric tumor growth in vivo.
• Tumor suppression was attributed to chemotactic autoimmune cell infiltration and T cell activation.

Conclusions:

• The HCI fusion protein represents a promising, less toxic, and lower-cost therapeutic strategy for HER-2 positive gastric tumors.
• This recombinant protein technology offers an attractive alternative to current HER-2 targeted therapies.
• The HCI fusion protein has potential for subsequent clinical application in treating HER-2 positive gastric cancers.