<p>Re-arming the immune system to fight cancer holds significant promise. However, models enabling the rapid and reliable evaluation of immunotherapies on patient tumors are still lacking. Here, we report a humanized version of the avian model for cell and patient-derived xenograft models, which involves the creation of miniature replicas of patient and cell line-derived tumors in avian embryo tissues. Leveraging this unique technology, we developed two approaches: co-micro-implantation of human PBMCs and cancer cells or implantation of cancer cells followed by the intravenous injection of human PBMCs. By combining whole-embryo light sheet microscopy, analysis of immune cell molecular markers and evaluation of anti-PD-1 therapy in solid tumor models, we demonstrate that the humanized AVI technology recapitulates an immune microenvironment, enables the rapid screening of immune-based therapeutic strategies and supports patient response stratification for biomarker discovery.</p>

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Humanized avian embryo models replicate an immune tumor environment for rapid immunotherapy studies

  • Marjorie Lacourrège,
  • Loraine Jarrosson,
  • Clélia Costechareyre,
  • Mathis Marcel,
  • Audrey Prunet,
  • Mayrone Mongellaz,
  • Camille Futelot,
  • Cyrus Rouhani,
  • Huong Giang Nguyen,
  • Thomas Aparicio,
  • Lionel Le Bourhis,
  • Céline Delloye-Bourgeois,
  • Romain Teinturier,
  • Valérie Castellani

摘要

Re-arming the immune system to fight cancer holds significant promise. However, models enabling the rapid and reliable evaluation of immunotherapies on patient tumors are still lacking. Here, we report a humanized version of the avian model for cell and patient-derived xenograft models, which involves the creation of miniature replicas of patient and cell line-derived tumors in avian embryo tissues. Leveraging this unique technology, we developed two approaches: co-micro-implantation of human PBMCs and cancer cells or implantation of cancer cells followed by the intravenous injection of human PBMCs. By combining whole-embryo light sheet microscopy, analysis of immune cell molecular markers and evaluation of anti-PD-1 therapy in solid tumor models, we demonstrate that the humanized AVI technology recapitulates an immune microenvironment, enables the rapid screening of immune-based therapeutic strategies and supports patient response stratification for biomarker discovery.