A novel fully human antitumour immunoRNase targeting ErbB2-positive tumours

Area of Science:

• Oncology
• Immunotherapy
• Biochemistry

Background:

• ErbB2 is a key target in cancer immunotherapy due to its overexpression on tumor cells.
• Trastuzumab, an anti-ErbB2 antibody, faces challenges including cardiotoxicity and treatment resistance.
• Novel therapeutic strategies are needed to overcome limitations of current ErbB2-targeted treatments.

Purpose of the Study:

• To design and characterize a novel human immunoRNase targeting ErbB2-positive tumors.
• To evaluate the efficacy and safety of the immunoRNase in preclinical models.

Main Methods:

• A novel immunoRNase, Erb-hcAb-RNase, was constructed by fusing an anti-ErbB2 compact antibody (Erb-hcAb) with human pancreatic RNase (HP-RNase).
• The immunoRNase was expressed in mammalian cells, purified, and characterized for enzymatic activity and binding affinity.
• Biological activity was assessed in vitro and in vivo on ErbB2-positive tumor cells.

Main Results:

• Erb-hcAb-RNase demonstrated retained HP-RNase enzymatic activity and specific binding to ErbB2-positive cells.
• The immunoRNase exhibited potent and selective antiproliferative effects on ErbB2-positive tumor cells in vitro and in vivo.
• Erb-hcAb-RNase showed enhanced anti-tumor activity compared to the parental antibody due to combined cytotoxic mechanisms.

Conclusions:

• Erb-hcAb-RNase represents a promising novel therapeutic candidate for ErbB2-positive tumors.
• The dual mechanism of action (antibody-mediated targeting and RNase-induced cytotoxicity) offers a potential advantage.
• Further investigation is warranted for clinical development in ErbB2-positive cancer immunotherapy.