Antigen-Binding Molecule for Overcoming Immune Tolerance
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Solution Overview
Problem
Current methods for inducing strong antibody production against cancer cells face challenges due to immune tolerance and the difficulty in distinguishing self and non-self antigens, limiting the effectiveness of cancer immunotherapy.
Innovation Solution
Development of antigen-binding molecules that combine a domain binding to immune response-suppressing cells with a T cell receptor complex-binding domain to enhance humoral immunity, allowing for the production of antibodies against immunogens and their use in therapeutic vaccines.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If animal immunization methods are used to produce antibodies against cancer cells, then antibody production can be induced, but strong antibody production is difficult when the antigen is highly homologous to autologous proteins due to immune tolerance
Solution Approach 1:
The patent extracts and eliminates regulatory T cells (which suppress immune responses) from the immunized animal before harvesting antibodies. This is achieved by administering anti-CD25 antibodies that selectively bind to and remove regulatory T cells expressing the CD25 marker, thereby removing the suppressive influence that prevents strong antibody production against self-similar cancer antigens
Solution Approach 2:
The patent applies preliminary action by suppressing or eliminating regulatory T cells before the antibody production process is completed. By removing these immune-suppressing cells in advance through anti-CD25 antibody treatment, the system prepares the immune environment to allow strong humoral immune responses against self-similar antigens that would otherwise be tolerized
2Quantity of substance
If adjuvants such as TLR agonists are administered to induce strong humoral immunity, then antibody production is enhanced, but the complexity of the immunization protocol increases
Solution Approach 1:
Instead of adding complex adjuvants to stimulate the immune system, the patent takes out the suppressive elements (regulatory T cells) that are preventing strong antibody production. This simplification approach removes the need for complex adjuvant formulations and multiple injection protocols, achieving enhanced humoral immunity through selective elimination of immune-suppressing cells
3Quantity of substance
If regulatory T cells are suppressed to enhance humoral immune response, then antibody production against immunogens is improved, but the need for additional therapeutic interventions increases
Solution Approach 1:
The patent merges the antibody production process with the regulatory T cell suppression strategy into a single integrated therapeutic approach. The anti-CD25 antibody treatment is administered concurrently with or prior to immunization, combining the elimination of immune-suppressing cells with the induction of humoral immunity in one unified protocol, thereby producing antibodies against immunogens while simultaneously removing the need for separate therapeutic interventions
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach effectively enhances humoral immune responses and improves antibody production against cancer-specific antigens, overcoming immune tolerance and increasing antitumor activity.
Implementation Method 1
an antigen-binding molecule comprising: a domain that binds to a molecule expressed on a surface of a cell having an immune response-suppressing function, and a T cell receptor complex-binding domain
Implementation Method 2
methods for eliminating regulatory T cells expressing these antigens by Fc region-mediated ADCC activity
Data Source
AI summary
The present invention provides methods for producing antibodies against peptides, proteins, or such to which immune tolerance is easily established, by using antigen-binding molecules comprising a domain that binds to a molecule expressed on the surface of a cell having an immune response-suppressing function and a T cell receptor (TCR) complex-binding domain. The present invention also provides pharmaceutical compositions for use in combination with therapeutic vaccines and agents for enhancing a humoral immune response, each comprising the antigen-binding molecules as active ingredients.