# Exploring the Combined Action of Adding Pertuzumab to Branded Trastuzumab versus Trastuzumab Biosimilars for Treating HER2+ Breast Cancer

## TL;DR

This study compares how trastuzumab biosimilars and branded trastuzumab interact with HER2 in breast cancer when combined with pertuzumab.

## Contribution

The study reveals that trastuzumab biosimilars behave similarly to branded trastuzumab in complex formation with HER2 when combined with pertuzumab.

## Key findings

- Trastuzumab molecules, including biosimilars, show analogous binding behavior to HER2 in the presence of pertuzumab.
- Adding HER2 to a mixture of trastuzumab and pertuzumab increases high-order HER2 complex formation significantly.
- The observed complex formation suggests a potential synergistic effect that could improve treatment efficacy for HER2-positive cancers.

## Abstract

The binding activity of various trastuzumab biosimilars versus the branded trastuzumab towards the glycosylated extracellular domain of the human epidermal growth factor receptor 2 (HER2) target in the presence of pertuzumab was investigated. We employed size exclusion chromatography with tetra-detection methodology to simultaneously determine absolute molecular weight, concentration, molecular size, and intrinsic viscosity. All trastuzumab molecules in solution exhibit analogous behavior in their binary action towards HER2 regardless of the order of addition of trastuzumab/pertuzumab. This analogous behavior of all trastuzumab molecules, including biosimilars, highlights the robustness and consistency of their binding activity towards HER2. Furthermore, the addition of HER2 to a mixture of trastuzumab and pertuzumab leads to increased formation of high-order HER2 complexes, up to concentrations of one order of magnitude higher than in the case of sequential addition. The observed increase suggests a potential synergistic effect between these antibodies, which could enhance their therapeutic efficacy in HER2-positive cancers. These findings underscore the importance of understanding the complex interplay between therapeutic antibodies and their target antigens, providing valuable insights for the development of more effective treatment strategies.