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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1505868
This article is part of the Research Topic Crosstalk in Tumor Microenvironments: Shaping Early Drug and Immunotherapy Strategies View all 5 articles

Developing Transcriptomic Biomarkers for TAVO412 Utilizing Next Generation Sequencing Analyses of Preclinical Tumor Models

Provisionally accepted
Mark L Chiu Mark L Chiu 1*Ying Jin Ying Jin 1,2Peng Chen Peng Chen 2Huajun Zhou Huajun Zhou 3Guangmao Mu Guangmao Mu 2Simin Wu Simin Wu 2Zhengxia Zha Zhengxia Zha 2Bin Ma Bin Ma 2Chao Han Chao Han 1
  • 1 Tavotek Biotherapeutics, Lower Gwynedd, United States
  • 2 Tavotek Biotherapeutics Suzhou, Suzhou, Liaoning Province, China
  • 3 Crown Bioscience (China), Beijing, Beijing Municipality, China

The final, formatted version of the article will be published soon.

    TAVO412, a multi-specific antibody targeting epidermal growth factor receptor (EGFR), mesenchymal epithelial transition factor (c-Met), and vascular endothelial growth factor A (VEGF-A), is undergoing clinical development for the treatment of solid tumors. TAVO412 has multiple mechanisms of action for tumor growth inhibition that include shutting down the EGFR, c-Met, and VEGF signaling pathways, having enhanced Fc effector functions, addressing drug resistance that can be mediated by the crosstalk amongst these three targets, as well as inhibiting angiogenesis. TAVO412 demonstrated strong in vivo tumor growth inhibition in 23 cell-line derived xenograft (CDX) models representing diverse cancer types, as well as in 9 patient-derived xenograft (PDX) lung tumor models. Using preclinical CDX data, we established transcriptomic biomarkers based on gene expression profiles that were correlated with anti-tumor response or distinguished between responders and non-responders. Together with specific driver mutation that associated with efficacy and the targets of TAVO412, a set of 21-gene biomarker was identified to predict the efficacy. A biomarker predictor was formulated based on the Linear Prediction Score (LPS) to estimate the probability of patients or tumor model response to TAVO412 treatment. This efficacy predictor for TAVO412 demonstrated 78% accuracy in the CDX training models. The biomarker model was further validated in the PDX data set and resulted in comparable accuracy.In implementing precision medicine by leveraging preclinical model data, a predictive transcriptomic biomarker empowered by next-generation sequencing was identified that could optimize the selection of patients that may benefit most from TAVO412 treatment.

    Keywords: EGFR cancer cells +, cmet, VEGF - vascular endothelial growth factor, trispecific antibodies, PDX (patient derived xenograft), CDx, Transcriptome

    Received: 03 Oct 2024; Accepted: 15 Jan 2025.

    Copyright: © 2025 Chiu, Jin, Chen, Zhou, Mu, Wu, Zha, Ma and Han. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Mark L Chiu, Tavotek Biotherapeutics, Lower Gwynedd, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.