In vitro vascularized immunocompetent patient-derived model to test cancer therapies
Hélène Lê,
Jules Deforges,
Guoqiang Hua,
Ysia Idoux-Gillet,
Charlotte Ponté,
Véronique Lindner,
Anne Olland,
Pierre-Emanuel Falcoz,
Cécile Zaupa,
Shreyansh Jain,
Eric Quéméneur,
Nadia Benkirane-Jessel,
Jean-Marc Balloul
Affiliations
Hélène Lê
Transgene S.A, 400 Boulevard Gonthier d’Andernach, 67400 Illkirch-Graffenstaden, France; INSERM UMR 1260, Regenerative Nanomedicine, 1 rue Eugène Boeckel, 67000 Strasbourg, France
Jules Deforges
Transgene S.A, 400 Boulevard Gonthier d’Andernach, 67400 Illkirch-Graffenstaden, France
Guoqiang Hua
INSERM UMR 1260, Regenerative Nanomedicine, 1 rue Eugène Boeckel, 67000 Strasbourg, France
Ysia Idoux-Gillet
INSERM UMR 1260, Regenerative Nanomedicine, 1 rue Eugène Boeckel, 67000 Strasbourg, France
Charlotte Ponté
INSERM UMR 1260, Regenerative Nanomedicine, 1 rue Eugène Boeckel, 67000 Strasbourg, France; Hopitaux Universitaires de Strasbourg, 1 Place de l’Hôpital, 67000 Strasbourg, France
Véronique Lindner
INSERM UMR 1260, Regenerative Nanomedicine, 1 rue Eugène Boeckel, 67000 Strasbourg, France
Anne Olland
INSERM UMR 1260, Regenerative Nanomedicine, 1 rue Eugène Boeckel, 67000 Strasbourg, France; Hopitaux Universitaires de Strasbourg, 1 Place de l’Hôpital, 67000 Strasbourg, France
Pierre-Emanuel Falcoz
INSERM UMR 1260, Regenerative Nanomedicine, 1 rue Eugène Boeckel, 67000 Strasbourg, France; Hopitaux Universitaires de Strasbourg, 1 Place de l’Hôpital, 67000 Strasbourg, France
Cécile Zaupa
Boehringer Ingelheim, 29 avenue Tony Garnier, 69007 Lyon, France
Shreyansh Jain
Transgene S.A, 400 Boulevard Gonthier d’Andernach, 67400 Illkirch-Graffenstaden, France
Summary: This work describes a patient-derived tumoroid model (PDTs) to support precision medicine in lung oncology. The use of human adipose tissue-derived microvasculature and patient-derived peripheral blood mononuclear cells (PBMCs) permits to achieve a physiologically relevant tumor microenvironment. This study involved ten patients at various stages of tumor progression. The vascularized, immune-infiltrated PDT model could be obtained within two weeks, matching the requirements of the therapeutic decision. Histological and transcriptomic analyses confirmed that the main features from the original tumor were reproduced. The 3D tumor model could be used to determine the dynamics of response to antiangiogenic therapy and platinum-based chemotherapy. Antiangiogenic therapy showed a significant decrease in vascular endothelial growth factor (VEGF)-A expression, reflecting its therapeutic effect in the model. In an immune-infiltrated PDT model, chemotherapy showed the ability to decrease the levels of lymphocyte activation gene-3 protein (LAG-3), B and T lymphocyte attenuator (BTLA), and inhibitory receptors of T cells functions.
