Avian CAM Model for Rapid Circulating Tumor Cell Amplification
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Solution Overview
Problem
Current methods for amplifying circulating tumor cells (CTC) are expensive and time-consuming, often requiring in vitro expansion before in vivo models, which are not compatible with clinical practice and can lead to phenotype modifications.
Innovation Solution
An avian model using embryonated bird's eggs, preferably chicken eggs, where CTCs are grafted onto the chorioallantoic membrane (CAM) at a specific developmental stage, allowing direct amplification and development of tumors for testing therapeutic agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If in vitro expansion or murine models are used to amplify CTC, then CTC amplification is achieved, but the process becomes expensive and time-consuming
Solution Approach 1:
The patent uses embryonated chicken eggs as a disposable, inexpensive in ovo model system to amplify CTC. Each egg serves as a single-use bioreactor that can be discarded after the amplification process, eliminating the need for expensive and time-consuming in vitro expansion or immunodeficient mouse models. The eggs provide a ready-made vascularized environment that supports rapid CTC proliferation without requiring complex infrastructure.
Solution Approach 2:
The invention changes the biological system parameter from mammalian (in vitro or mouse models) to avian (chicken egg) model. This parameter change enables faster CTC amplification kinetics and reduces costs while maintaining the ability to generate sufficient CTC numbers for downstream applications. The avian model provides a different physiological environment that accelerates the amplification process compared to traditional methods.
2Quantity of substance
If in vitro expansion is performed before in vivo models, then CTC amplification is achieved, but phenotype modifications occur
Solution Approach 1:
The chicken egg serves as an intermediary in vivo environment that bridges the gap between in vitro expansion and direct patient treatment. Instead of expanding CTC in artificial in vitro conditions that cause phenotype drift, the cells are introduced into the egg where they amplify in a more physiological environment. This intermediary step preserves the original CTC phenotype while achieving the necessary amplification for therapeutic applications.
Solution Approach 2:
The patent performs preliminary amplification of CTC in the chicken egg model before therapeutic intervention. This preliminary action in a controlled in ovo environment allows sufficient CTC expansion to occur while maintaining phenotype stability, preparing the cells for subsequent treatment without requiring prolonged in vitro culture that would compromise cell characteristics.
3Quantity of substance
If immunodeficient mice are used as incubators for CTC, then CTC amplification is achieved, but the cost increases significantly
Solution Approach 1:
The patent replaces expensive immunodeficient mice with inexpensive embryonated chicken eggs as the amplification medium. Each egg is a low-cost, disposable unit that eliminates the need for maintaining costly animal facilities and specialized care protocols. The eggs can be obtained at minimal cost and used once for CTC amplification, making the process economically viable for routine clinical applications.
Solution Approach 2:
The invention creates a simplified copy of the in vivo amplification environment using the chicken egg model, which replicates the essential features needed for CTC proliferation without the complexity and cost of immunodeficient mouse systems. The egg provides a surrogate physiological environment that captures the necessary conditions for CTC growth while eliminating the expensive immunological components.
Data Source
AI summary
The present invention relates to an avian model enabling the amplification of human or animal circulating tumour cells (CTC) and to the use thereof for monitoring and determining the sensitivity of a patient or an animal suffering from cancer to one or more therapeutic agent(s), as well as for screening novel therapeutic agents intended for the treatment of cancer.