A Face-To-Face Comparison of Tumor Chicken Chorioallantoic Membrane (TCAM) In Ovo with Murine Models for Early Evaluation of Cancer Therapy and Early Drug Toxicity

Abstract

Ethical considerations, cost, and time constraints have highlighted the need to develop alternatives to rodent in vivo models for evaluating drug candidates for cancer. The tumor chicken chorioallantoic membrane (TCAM) model provides an affordable and fast assay that permits direct visualization of tumor progression. Tumors from multiple species including rodents and human cell lines can be engrafted. In this study, we engrafted several tumor models onto the CAM and demonstrated that the TCAM model is an alternative to mouse models for preliminary cancer drug efficacy testing and toxicity analysis. Tumor cells were deposited onto CAM, and then grown for up to an additional 10 days before chronic treatments were administered. The drug response of anticancer therapies was screened in 12 tumor cell lines including glioblastoma, melanoma, breast, prostate, colorectal, liver, and lung cancer. Tumor-bearing eggs and tumor-bearing mice had a similar chemotherapy response (cisplatin and temozolomide) in four human and mouse tumor models. We also demonstrated that lethality observed in chicken embryos following chemotherapies such as cisplatin and cyclophosphamide were associated with corresponding side-effects in mice with body weight loss. According to our work, TCAM represents a relevant alternative model to mice in early preclinical oncology screening, providing insights for both the efficacy and the toxicity of anticancer drugs.

The Chorioallantoic Membrane Xenograft Assay as a Reliable Model for Investigating the Biology of Breast Cancer

“…To date, comparisons between different xenograft models are lacking in the literature. However, there are few studies for the biomarker assessment in glioblastomas [ 81 ] and human epidermoid carcinoma cell line (HEp3) [ 82 , 83 ] and for the early evaluation of cancer therapy and early drug toxicity [ 84 ], which already shows that the CAM model is an excellent alternative for in vivo studies.…”

Evaluation of Temozolomide and Fingolimod Treatments in Glioblastoma Preclinical Models

“…The cell culture procedure was carried out according to previous work [ 28 , 51 ]. U118MG human glioblastoma cells (HTB-15™ obtained from ATCC ® , Manassas, VA, USA), GL261 mouse glioma cells (ACC 802 obtained from Leibniz Institute DMSZ), U138MG human glioblastoma cells (HTB-16™ obtained from ATCC ® , Manassas, VA, USA), and U87MG human glioblastoma cells (ECACC 89081402™ obtained from ATCC ® , Manassas, VA, USA) were cultured with RPMI 1640 (Gibco ® , Billings, MT, USA, ATCC-formulated) supplemented with fetal bovine serum (FBS, Gibco ® ) at a final concentration of 10% including antibiotics (Penicillin 100 U/mL-Streptomycin 100 µg/mL, Gibco ® ).…”

“…The GL261-Luc cells (transduced with lentiviral vector 79692-G from AMSBIO) expressing luciferase (Luc) were cultured in RPMI medium as described above, including 100 μg/mL of G418/Geneticin. All procedures were performed under aseptic conditions as previously described [ 28 , 51 ]. Cells were grown at 37 °C and 5% CO 2 and they did not expand beyond 8 passages in culture.…”

Editorial for Special Issue: The Chorioallantoic Membrane (CAM) Model—Traditional and State-of-the Art Applications: The 1st International CAM Conference

“…What we need for replacement strategies are more direct comparisons between the CAM and the mouse models for specific applications. In this regard, Rupp et al treated a large panel of different human and mouse tumor cell lines with clinically approved anti-cancer drugs and demonstrated similar effects in both mice and chicken embryo xenografts [11]. The INOVOTION team described new and impressive applications in the field of immune oncology.…”