Abstract 6907: Micro-implantation of patient tumor samples into the avian embryo, a fast and reliable alternative in vivo technology for preclinical studies on melanoma and follicular lymphoma

Abstract

Abstract Despite recent efforts to develop reliable and predictive patient-derived cancer models, drug attrition rates in oncology remain high. Moreover, conventional models such as patient-derived xenograft (PDX) mouse models face major cost and time limitations, not supporting real-time clinical decision making. To overcome such limitation, ONCOFACTORY developed a proprietary PDX platform enabling the engraftment of small size tumor biopsy samples within targeted tissue of the avian embryo at early stage of development, to conduct preclinical proof of efficacy studies and provide PDX clinical trial solution helping with patient’s selection prior to clinical phase II/III. On one hand, we performed prospective co-clinical trial aiming to evaluate the utility of the AVI-PDXTM model in predicting the response to standard therapy, consisting of BRAF and MEK inhibitors, for patient with metastatic melanoma harboring BRAF mutations. Skin biopsy samples were implanted into specific tissue driving tumor formation under the skin of avian embryos. On the other hand, we conducted a retrospective cohort study with 20 follicular lymphoma (FL) patient samples divided into “partial” and “complete” responders to the standard immuno-chemotherapy RCHOP regimen to establish FL AVI-PDXTM, and examine sensitivity to RCHOP in ovo. Twenty-four hours post-implantation, avian melanoma and FL replicas were respectively exposed to BRAFi/MEKi or RCHOP and their vehicles, over 24h. Then, embryos were harvested, and tumor response was examined by measuring tumor volume using light sheet microscopy. Alongside, in independent series of avian embryos implanted with FL samples, tumors were harvested for single-cell transcriptomic analyses to explore mechanism of response to RCHOP. For melanoma, we provide the proof of concept that the AVI-PDXTM reliably predict sensitivity or resistance to BRAF and MEK inhibitors within days, matching patient clinical outcome observed in clinic. For FL, we showed that the FL-AVI-PDXTM efficiently captures clinical response to RCHOP in a heterogenous cohort of patients, enabling to discriminate partial and complete responder within short-time frame. Next, we identified a robust genetic signature reflecting exposure of tumoral cells to RCHOP and showed that drug-mediated targeting of one of these genes with a chemotherapy resulted in strong potentiation of RCHOP. Thus, we provide evidence of the high predictive power of the AVI-PDXTM models allowing fast and reproducible generation of tumors replicas from small size patient tumor samples. This places the AVI-PDXTM as a valuable tool for clinical research to rationalize patient inclusion in clinical trials but also for the design of personalized medicine assays. Citation Format: Clelia Costechareyre, Loraine Jarrosson, Marjorie Lacourrege, Romain Teinturier, Julie Caramel, Manon Zala, Stéphane Dalle, Pierre Sujobert, Céline Delloye-Bourgeois, Frédéric Berget, Valérie Castellani. Micro-implantation of patient tumor samples into the avian embryo, a fast and reliable alternative in vivo technology for preclinical studies on melanoma and follicular lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6907.