Antibody Generation from Resistant Tumor Homogenate
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Solution Overview
Problem
Current methods for generating antibodies, particularly monoclonal antibodies, are limited in addressing resistance mechanisms developed by tumors after anti-tumoral treatments, as they rely on known antigens and do not effectively target antigens expressed by resistant tumors.
Innovation Solution
The use of a milled homogenate or suspension from resistant tumors to immunize animals, generating antibodies that recognize antigens specifically expressed on resistant tumor cells but not on native tumor cells, potentially involved in treatment resistance, through a process involving tolerization and differential immunohistochemistry screening.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If conventional antibody generation methods using known antigens are used, then the antibody generation process is straightforward and reliable, but the antibodies cannot target antigens expressed by resistant tumors
Solution Approach 1:
Instead of using known antigens from native tumors to generate antibodies, the invention inverts the approach by using antigens from resistant tumors as the immunization source. This allows the generated antibodies to specifically recognize and bind to resistance-associated antigens that are not targeted by conventional methods.
Solution Approach 2:
The invention performs preliminary tolerization of the immune system using native tumor antigens before immunization with resistant tumor antigens. This preliminary action prevents the immune system from rejecting the resistant tumor antigens while still enabling specific antibody generation against resistance-associated epitopes.
2Measurement precision
If antibodies are generated against all tumor antigens, then broad recognition is achieved, but specificity for resistance-associated antigens is lost
Solution Approach 1:
The screening process is segmented into two distinct stages: first screening for antibodies that recognize resistant tumor antigens, then secondarily screening to exclude antibodies that also recognize native tumor antigens. This segmentation enables precise identification of antibodies with specific binding to resistance-associated antigens.
Solution Approach 2:
The differential screening process provides feedback by comparing antibody binding to both native and resistant tumors. Antibodies showing binding to native tumors are excluded, while those binding only to resistant tumors are selected, ensuring high specificity for resistance-associated antigens.
Data Source
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AI summary
The present invention relates to the use of a milled homogenate and/or a suspension and/or a cell lysate, stemming from a tumor resistant to at least one antitumoral compound in order to immunize and generate in vitro an antibody, or one of its functional fragments, directed against a tumoral antigen specifically expressed at the surface of said resistant tumor and being possibly involved in the resistance of said resistant tumor. More particularly, the present invention is directed to such antibodies obtained by applying the method, such as the antibodies 1A6, 1A9, 2E11, 3C11 and 3G7, as well as to their use for treating cancer.