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PreprintCC BY-NCbioRxiv

A Multiplex Protein Microarray Platform for Preclinical Tissue Binding and Cross-Reactivity of Therapeutic Antibodies

  1. 1JeiserBio inc.

Abstract

The NexAb multiplex protein microarray platform, comprising a 7,015-spot tissue lysate array and antigen-oriented protein arrays, was developed for preclinical tissue-binding and cross-reactivity assessment of therapeutic antibodies. Four anti-HER2 antibodies, trastuzumab, pertuzumab, trastuzumab emtansine (T-DM1), and trastuzumab deruxtecan (T-DXd), were profiled with integrated ERBB2 mRNA data. On antigen-oriented arrays, cell-synthesized HER2 bound trastuzumab and pertuzumab strongly and epitope-dependently, whereas wheat-germ HER2 showed no binding. On the tissue lysate array, trastuzumab and T-DM1 bound HER2-positive cancer cell lines and tumor tissues with nearly identical profiles (correlation coefficient r = 0.991), and T-DXd bound ERBB2-low cancer spots and 38.8% of normal human tissue spots, a profile not conserved in cynomolgus monkeys. Trastuzumab, T-DM1, and pertuzumab showed no cross-reactivity with cynomolgus monkey tissues, whereas T-DXd bound 3.1% of monkey tissue spots. NexAb enables quantitative cross-reactivity profiling relevant to preclinical safety evaluation.

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BibTeX
@misc{matsukura2026multiplex,
  title = {{A Multiplex Protein Microarray Platform for Preclinical Tissue Binding and Cross-Reactivity of Therapeutic Antibodies}},
  author = {S. Matsukura and N. Sawada and M. Watanabe and I. Yabuta and G. Morisawa and Y. Kawamura and H. Nanamiya and J.-i. Imai and M. Takagi},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.11.757820},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.11.757820v1},
  note = {CC BY-NC},
}
RIS
TY  - UNPB
TI  - A Multiplex Protein Microarray Platform for Preclinical Tissue Binding and Cross-Reactivity of Therapeutic Antibodies
AU  - S. Matsukura
AU  - N. Sawada
AU  - M. Watanabe
AU  - I. Yabuta
AU  - G. Morisawa
AU  - Y. Kawamura
AU  - H. Nanamiya
AU  - J.-i. Imai
AU  - M. Takagi
PY  - 2026
DA  - 2026/10/11
PB  - bioRxiv
DO  - 10.64898/2026.10.11.757820
UR  - https://www.biorxiv.org/content/10.64898/2026.10.11.757820v1
AB  - The NexAb multiplex protein microarray platform, comprising a 7,015-spot tissue lysate array and antigen-oriented protein arrays, was developed for preclinical tissue-binding and cross-reactivity assessment of therapeutic antibodies. Four anti-HER2 antibodies, trastuzumab, pertuzumab, trastuzumab emtansine (T-DM1), and trastuzumab deruxtecan (T-DXd), were profiled with integrated ERBB2 mRNA data. On antigen-oriented arrays, cell-synthesized HER2 bound trastuzumab and pertuzumab strongly and epitope-dependently, whereas wheat-germ HER2 showed no binding. On the tissue lysate array, trastuzumab and T-DM1 bound HER2-positive cancer cell lines and tumor tissues with nearly identical profiles (correlation coefficient r = 0.991), and T-DXd bound ERBB2-low cancer spots and 38.8% of normal human tissue spots, a profile not conserved in cynomolgus monkeys. Trastuzumab, T-DM1, and pertuzumab showed no cross-reactivity with cynomolgus monkey tissues, whereas T-DXd bound 3.1% of monkey tissue spots. NexAb enables quantitative cross-reactivity profiling relevant to preclinical safety evaluation.
ER  -