Developing transcriptomic biomarkers for TAVO412 utilizing next generation sequencing analyses of preclinical tumor models
IntroductionTAVO412, 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 mechanism...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1505868/full |
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| author | Ying Jin Peng Chen Huajun Zhou Guangmao Mu Simin Wu Zhengxia Zha Bin Ma Chao Han Mark L. Chiu Mark L. Chiu |
| author_facet | Ying Jin Peng Chen Huajun Zhou Guangmao Mu Simin Wu Zhengxia Zha Bin Ma Chao Han Mark L. Chiu Mark L. Chiu |
| author_sort | Ying Jin |
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| description | IntroductionTAVO412, 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.MethodsUsing 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. ResultsThis 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. ConclusionsIn 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. |
| format | Article |
| id | doaj-art-772ece8a4b66455887040db9645c2797 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-772ece8a4b66455887040db9645c27972025-02-10T05:16:04ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15058681505868Developing transcriptomic biomarkers for TAVO412 utilizing next generation sequencing analyses of preclinical tumor modelsYing Jin0Peng Chen1Huajun Zhou2Guangmao Mu3Simin Wu4Zhengxia Zha5Bin Ma6Chao Han7Mark L. Chiu8Mark L. Chiu9Research & Development Department, Tavotek Biotherapeutics, Suzhou, Jiangsu, ChinaResearch & Development Department, Tavotek Biotherapeutics, Suzhou, Jiangsu, ChinaGlobal Center for Data Science and Bioinformatics, Crown Bioscience Inc., Suzhou, Jiangsu, ChinaResearch & Development Department, Tavotek Biotherapeutics, Suzhou, Jiangsu, ChinaResearch & Development Department, Tavotek Biotherapeutics, Suzhou, Jiangsu, ChinaResearch & Development Department, Tavotek Biotherapeutics, Suzhou, Jiangsu, ChinaResearch & Development Department, Tavotek Biotherapeutics, Suzhou, Jiangsu, ChinaResearch & Development, Tavotek Biotherapeutics, Spring House, PA, United StatesResearch & Development Department, Tavotek Biotherapeutics, Suzhou, Jiangsu, ChinaResearch & Development, Tavotek Biotherapeutics, Spring House, PA, United StatesIntroductionTAVO412, 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.MethodsUsing 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. ResultsThis 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. ConclusionsIn 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. https://www.frontiersin.org/articles/10.3389/fimmu.2025.1505868/fullEGFR cancer cells +cmetVEGF - vascular endothelial growth factorantibodiesPDX (patient derived xenograft)CDx |
| spellingShingle | Ying Jin Peng Chen Huajun Zhou Guangmao Mu Simin Wu Zhengxia Zha Bin Ma Chao Han Mark L. Chiu Mark L. Chiu Developing transcriptomic biomarkers for TAVO412 utilizing next generation sequencing analyses of preclinical tumor models Frontiers in Immunology EGFR cancer cells + cmet VEGF - vascular endothelial growth factor antibodies PDX (patient derived xenograft) CDx |
| title | Developing transcriptomic biomarkers for TAVO412 utilizing next generation sequencing analyses of preclinical tumor models |
| title_full | Developing transcriptomic biomarkers for TAVO412 utilizing next generation sequencing analyses of preclinical tumor models |
| title_fullStr | Developing transcriptomic biomarkers for TAVO412 utilizing next generation sequencing analyses of preclinical tumor models |
| title_full_unstemmed | Developing transcriptomic biomarkers for TAVO412 utilizing next generation sequencing analyses of preclinical tumor models |
| title_short | Developing transcriptomic biomarkers for TAVO412 utilizing next generation sequencing analyses of preclinical tumor models |
| title_sort | developing transcriptomic biomarkers for tavo412 utilizing next generation sequencing analyses of preclinical tumor models |
| topic | EGFR cancer cells + cmet VEGF - vascular endothelial growth factor antibodies PDX (patient derived xenograft) CDx |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1505868/full |
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