PO.TB04.03 · 肿瘤生物学

3D bioprinting of fresh NSCLC: The Lung3Dprint proof of concept study

编号 4872 展板 21 时间 4/21 09:00–12:00 区域 Section 28 主讲 Aurélie Cadiou, Pharm D

分会场 In Vitro Models 2: 2D, 3D, Organoids, and Spheroids

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作者与单位

Aurélie Cadiou¹, Clarisse Thiollier-Schmitt¹, Gabrielle Devret², Raphaële Guelminger³, Tanguy Fenouil⁴, Corinne Perrin⁵, Camille Leonce¹, Samantha Ballesta⁶, Gaëtan Pochon⁶, Nicolas Alcala⁷, Lars Petter Jordheim¹, Charles Dumontet¹, Michaël Duruisseaux¹

¹Cancer Research Center of Lyon (CRCL), Lyon, France,²Service de chirurgie thoracique, Hôpital Louis Pradel, Hospices Civils de Lyon, Lyon, France,³Hospices Civils de Lyon, Lyon, France,⁴Groupement Hospitalier Est, Institut de Pathologie Multisite - Site Est, Hospices Civils de Lyon, Bron, France,⁵Groupement Hospitalier Est, Tissu-Tumorothèque Est, CRB HCL, Hospices Civils de Lyon, Bron, France,⁶3D-ONCO platform, Cancer Research Center of Lyon (CRCL), Lyon, France,⁷International Agency for Research on Cancer, Lyon, France

摘要 Abstract

3D bioprinted models are emerging to bridge the gap between 2D systems and animal models, advancing the efficiency and accuracy of preclinical workflows. This work aimed to (i) develop an innovative methodology to generate patient-derived bioprinted lung cancer (PDBLC) models that aim to reflect the heterogeneity of the parent tumor, and (ii) evaluate these models as a relevant ex vivo drug screening tool. Fresh Non-Small Cell Lung Cancer (NSCLC) samples were obtained from March to October 2025 at Hospices Civils de Lyon, dissociated and embedded into a fibrinogen-alginate-gelatin bioink (0.5 to 5x10 6 cells/mL of bioink). PDBLC models were obtained by extrusion-based bioprinting using a Cellink BIO X TM , with post-conditioning polymerization using thrombin, transglutaminase, and calcium. PDBLC models were then placed in a dedicated lung cancer cell culture medium and analyzed at different time points, using a non-disruptive method (PrestoBlue TM assay) and disruptive methods (flow cytometry and immunohistochemistry). Flow cytometry markers include EpCAM and CK-7/-8 to identify tumor cells, CD31 for endothelial cells, CD45, CD3, and CD19 for leukocyte infiltrate, and FAP, ɑ-SMA and PDGFR-beta for analysis of cancer-associated fibroblasts. Tumor and non-tumor cell contents were quantified as number of cells per object and their percentage of total live cells present. Nine samples have presently been bioprinted and analyzed. PrestoBlue TM assay enabled non-specific monitoring of the model's metabolic activity over time. The median percentage of tumor cells in the bioink was estimated at 40% (range: 11 - 85). The percentage of viable tumor cells on days 7 and 14 were dependent on the initial concentration of cells in the bioink, ranging from 5 to 84%. The absolute number of tumor cells per PDBLC model tended to stabilize with time. The absolute percentage of viable tumor cells tended to increase between day 0 and day 14, with a median fold-change of 1.7-fold (range: -0.76 - 7.2). This was notably due to the decrease in the leukocyte infiltration as well as the endothelial subpopulation. Leukocyte subpopulation remaining 14 days after bioprinting was found to be T lymphocytes (CD45+ CD3+). Exposure of PDBLC models to conventional and targeted therapies used in NSCLC patients is ongoing and results will be presented. 3D bioprinting offers a relatively inexpensive and rapid means to evaluate fresh tumor samples. Our preliminary data show that our model not only supports fresh NSCLC cell survival for up to 22 days, but also maintains the primary tumor's heterogeneity over this period. The use of these 3D models as a drug-screening platform is being evaluated and would be relevant for translational research and clinical practice.

利益披露 Disclosure

A. Cadiou, None.. C. Thiollier-Schmitt, None.. G. Devret, None.. R. Guelminger, None.. T. Fenouil, None.. C. Perrin, None.. C. Leonce, None.. S. Ballesta, None.. G. Pochon, None.. L. Jordheim, None.. C. Dumontet, None. M. Duruisseaux, Pfizer g., Board of Directors, non-salaried role), ), Other, Remuneration for participation in scientific meetings. Merus ). Takeda g., Board of Directors, non-salaried role), ). Guardant g., Board of Directors, non-salaried role), ), Other, Remuneration for participation in scientific meetings. Eli Lilly ). Boehringer Ingelheim g., Board of Directors, non-salaried role), Other, Remuneration for participation in scientific meetings. Astra Zeneca g., Board of Directors, non-salaried role), Other, Remuneration for participation in scientific meetings. Roche g., Board of Directors, non-salaried role), Other, Remuneration for participation in scientific meetings. BMS g., Board of Directors, non-salaried role), Other, Remuneration for participation in scientific meetings. Abbvie g., Board of Directors, non-salaried role). MSD g., Board of Directors, non-salaried role), Other, Remuneration for participation in scientific meetings. Novartis g., Board of Directors, non-salaried role), Other, Remuneration for participation in scientific meetings. GSK ). Sanofi g., Board of Directors, non-salaried role). Amgen g., Board of Directors, non-salaried role), Other, Remuneration for participation in scientific meetings. Regeneron g., Board of Directors, non-salaried role). Revolution Medecine g., Board of Directors, non-salaried role). Novocure g., Board of Directors, non-salaried role).

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