Abstract 1168: The “humanized” chicken embryo chorioallantoic membrane (CAM) as a personalized platform for high-throughput (HTP) screening of cancer therapeutics

2018 
Background Every day, millions of people are taking medications that will not help them. “Personalized medicine,” is the tailoring of medical treatment to a single person, shape his response to a particular treatment and aims to better target intervention, maximize benefit and minimize harm. Several techniques are available to grow primary cell cultures from tumors; however, very few have been found to be promising. Novel, cost-effective model that similarly mimic tumor biology and provide faster information on the activity of anticancer therapies could therefore make an important contribution to the advancement of personalized medicine. Chick Chorioallantoic Membrane (CAM) assays have been used to study the process and therapeutics involving angiogenesis, tumor cell invasion and metastasis. The CAM is naturally immuno-deficient and rich in vascularity therefore an ideal system, allowing to generate 3D cancerous “organoids” in a very efficient, reproducible and cost-effective manner and translates basic research to the clinic. Aim 1) Generate a “personalized medicine” HTP system for a quick and reliable evaluation of the effectiveness of different therapeutic options on of 3D "organoid" tumors; 2) Using the "humanized egg" as a low-cost and highly efficient mimetic of the mouse PDX model ". Methods Fertilized eggs were incubated until day 3 (37°C, 75-90% humidity). 2ml of albumin was pulled from the egg to separate the CAM membrane from the egg shell. Then, a small window in the egg shell has been made, and resealed with adhesive tape. On day 7, 3-5x106 tumor cells were transplanted onto the CAM membrane. The cancer cells become a visible tumor after 3 days. Different therapeutics (such as Erbitux, anti-CD24 mAb) were tested. Tumor growth was monitored by "live imaging" device. Results The efficiency and reproducibility of human cancer cell lines engraftment has been demonstrated. LV-GFP-Puro plasmid was constructed and used to generate GFP-encoded lentiviruses which then were used to generate a stable colorectal cancer cell line expressing GFP. The CAM tumors were evaluated histopathologicaly and IVIS fluorescent imaging. Anti-CD24 mAb inhibited tumor growth by ~70%.The presence of the humanized mAb in the engrafted tissue was confirmed by western blot analysis and IHC. Conclusions The ability to evaluate ex-vivo cancer tissue response to potential therapeutics in “humanized” settings within days is a very powerful tool. Citation Format: Shiran Shapira, Oren Bogin, Nadir Arber. The “humanized” chicken embryo chorioallantoic membrane (CAM) as a personalized platform for high-throughput (HTP) screening of cancer therapeutics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1168.
    • Correction
    • Source
    • Cite
    • Save
    • Machine Reading By IdeaReader
    0
    References
    0
    Citations
    NaN
    KQI
    []