Anti-T Cell Antibody CRS Mitigation via VEGF Inhibitor
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Solution Overview
Problem
Anti-T cell antigen-binding molecules, which target T cells to treat cancer, can cause adverse reactions such as cytokine release syndrome due to cytokine production, necessitating a solution to mitigate these effects.
Innovation Solution
Combining anti-T cell antigen-binding molecules with vascular endothelial growth factor (VEGF) inhibitors, which can be administered before, simultaneously, or after the antigen-binding molecules to prevent or alleviate cytokine release syndrome.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-T cell antigen-binding molecules are administered to treat cancer, then antitumor effects are improved, but cytokine release syndrome occurs causing adverse reactions
Solution Approach 1:
The patent applies preliminary anti-action by administering VEGF inhibitors before or concurrently with anti-T cell antigen-binding molecules to prevent cytokine release syndrome. The VEGF inhibitor pre-blocks the harmful cytokine release pathway, allowing subsequent administration of the anti-T cell antibody to exert antitumor effects without triggering severe CRS. This is evidenced by the patent's disclosure that VEGF inhibitor administration reduces IL-6 production and prevents CRS symptoms.
Solution Approach 2:
The patent uses VEGF inhibitors as an intermediary substance that mediates between the anti-T cell antigen-binding molecule and the harmful cytokine release response. The VEGF inhibitor acts as a protective intermediary that blocks the harmful pathway (cytokine release) while allowing the beneficial pathway (T cell-mediated cytotoxicity) to proceed. This intermediary approach enables the combination therapy to achieve both antitumor efficacy and reduced toxicity.
2Object-affected harmful factors
If VEGF inhibitor is administered to prevent cytokine release syndrome, then adverse reactions are reduced, but treatment complexity increases
Solution Approach 1:
The patent merges two therapeutic agents (VEGF inhibitor and anti-T cell antigen-binding molecule) into a single combination therapy regimen. Rather than treating CRS with separate rescue therapies after onset, the patent combines prophylactic VEGF inhibition with the anti-T cell antibody administration. This merging approach simplifies the overall treatment strategy by preventing CRS upfront rather than requiring multiple separate intervention steps.
Solution Approach 2:
The patent applies preliminary action by administering the VEGF inhibitor before or at the same time as the anti-T cell antigen-binding molecule to prevent CRS before it occurs. This preliminary blocking of the harmful pathway eliminates the need for subsequent rescue therapies, thereby reducing treatment complexity despite the addition of another agent. The patent specifies that VEGF inhibitor can be administered 1-7 days before, on the same day, or after the anti-T cell antibody.
Data Source
AI summary
The present disclosure provides methods for preventing, alleviating, or treating cytokine release resulting from administration of a VEGF inhibitor or side effects resulting from the cytokine release. To prevent, alleviate, or treat cytokine release or its side effects, the disclosure also provides combination therapies that use a lymphocyte-stimulating pharmaceutical agent, represented by an anti-T cell antigen-binding molecule, with a VEGF inhibitor. Among the anti-T cell antigen-binding molecules, for example, antibodies that recruit T cells as effector cells into tumor tissues are called T cell redirecting antibodies, and are known as means for treating tumors. On the other hand, when systemic cytokine production is stimulated by binding of antibodies to T cells, it is feared that this systemic action will lead to aberrations such as CRS. The present disclosure provides means for alleviating systemic cytokine production, and will enable safer use of anti-T cell antigen-binding molecules in tumor treatment.