In ovo model in cancer research and tumor immunology

Abstract

Considering cancer not only as malignant cells on their own but as a complex disease in which tumor cells interact and communicate with their microenvironment has motivated the establishment of clinically relevant 3D models in past years. Technological advances gave rise to novel bioengineered models, improved organoid systems, and microfabrication approaches, increasing scientific importance in preclinical research. Notwithstanding, mammalian in vivo models remain closest to mimic the patient’s situation but are limited by cost, time, and ethical constraints. Herein, the in ovo model bridges the gap as an advanced model for basic and translational cancer research without the need for ethical approval. With the avian embryo being a naturally immunodeficient host, tumor cells and primary tissues can be engrafted on the vascularized chorioallantoic membrane (CAM) with high efficiencies regardless of species-specific restrictions. The extraembryonic membranes are connected to the embryo through a continuous circulatory system, readily accessible for manipulation or longitudinal monitoring of tumor growth, metastasis, angiogenesis, and matrix remodeling. However, its applicability in immunoncological research is largely underexplored. Dual engrafting of malignant and immune cells could provide a platform to study tumor-immune cell interactions in a complex, heterogenic and dynamic microenvironment with high reproducibility. With some caveats to keep in mind, versatile methods for in and ex ovo monitoring of cellular and molecular dynamics already established in ovo are applicable alike. In this view, the present review aims to emphasize and discuss opportunities and limitations of the chicken embryo model for pre-clinical research in cancer and cancer immunology.

CARD11 gain of function upregulates BCL2A1 expression and promotes resistance to targeted therapies combination in B-cell lymphoma

“…To address MALT1/BCL2 dual targeting in CARD11 MUT MCL cells in vivo, we used the chick embryo chorioallantoic membrane (CAM). This vascularized and immunodeficient alternative in vivo model allows the growth of numerous cell types 36 . Here, we established a CAM model using BTK-resistant 37 CARD11 D230N BCL2A1 + PDX cells, which were treated with the clinically available MALT1 inhibitor JNJ-67856633 alone or in combination with the BCL2 inhibitor venetoclax (Fig.…”

“Centrosome Amplification promotes cell invasion via cell-cell contact disruption and Rap-1 activation”

“…To investigate how CA induction could initiate early tumourigenic change in vivo , we employed a chicken embryo xenograft model. The Chorioallantoic membrane assay (CAM assay), is a rapid, cost effective in vivo model for the study of tumourigenesis, angiogenesis, invasion and metastases (reviewed in (DeBord, 2018; Komatsu et al , 2019; Miebach et al , 2022; Ribatti, 2014). The CAM assay has been used to study angiogenesis and tumour cell invasion in breast, pancreatic, colorectal, prostate, brain and ovarian cancers using both human tumour cell line-derived xenografts as well as patient-derived xenografts (Aaltonen et al , 2022; Harper et al , 2021; Lokman et al , 2012).…”

Pancreatic Cancer Cells Undergo Immunogenic Cell Death upon Exposure to Gas Plasma-Oxidized Ringers Lactate

“…The tumor chorion-allantois model (TUM-CAM) for KPC960-GFP/Luc was established as described previously [21]. Briefly, pathogen-free, fertilized chicken eggs (Valo BioMedia, Osterholz-Scharmbeck, Germany) were incubated at 37 • C and 60% humidity in a dedicated breeding incubator (Hemel, Verl, Germany) for six days before the pointed pole was carefully punctured.…”