Chemoimmunotherapy for Epithelial Cancer via B Cell Depletion
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Solution Overview
Problem
Current cancer treatments face challenges in effectively targeting and eliminating large tumors due to immunosuppressive B cells that suppress cytotoxic T-cell activation, particularly in prostate and liver cancers, where these cells express IgA and PD-L1, leading to resistance against immunogenic chemotherapy like oxaliplatin.
Innovation Solution
Administering a combination of immunogenic chemotherapeutics, such as oxaliplatin, alongside antibodies that target and reduce the number or function of immunosuppressive B cells, including anti-CD19, anti-CD20, anti-PD-L1, and anti-CD19-CAR T cells, to induce immunogenic cell death and overcome B-cell-mediated immunosuppression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immunogenic chemotherapeutics like oxaliplatin are administered to induce immunogenic cell death, then tumor eradication is improved, but immunosuppressive B cells suppress cytotoxic T-cell activation leading to treatment resistance
Solution Approach 1:
The patent removes immunosuppressive B cells from the tumor microenvironment using targeted depletion strategies (anti-CD19, anti-CD20 antibodies) before administering immunogenic chemotherapy. This extraction of harmful immunosuppressive elements enables the chemotherapy to effectively activate cytotoxic T cells and eradicate tumors without being counteracted by B cell-mediated suppression.
Solution Approach 2:
The patent applies preliminary anti-action by depleting immunosuppressive B cells prior to chemotherapy administration. This pre-treatment prevents the anticipated harmful effect of B cell-mediated immunosuppression, allowing the subsequent immunogenic chemotherapy to proceed effectively without being blocked by tolerogenic mechanisms.
2Reliability
If high doses of chemotherapeutic agents are used to overcome B cell-mediated suppression, then tumor cell death is improved, but normal tissue toxicity increases
Solution Approach 1:
By extracting and removing immunosuppressive B cells through targeted depletion before chemotherapy, the patent eliminates the need for high-dose chemotherapeutic agents. This allows the use of lower, less toxic doses of chemotherapy while still achieving effective tumor cell death, as the B cell-mediated protective mechanism has been removed.
Solution Approach 2:
The patent introduces targeted depletion antibodies (anti-CD19, anti-CD20) as intermediaries that specifically eliminate B cells without directly affecting tumor cells or normal tissues. This intermediary approach removes the immunosuppressive barrier, allowing subsequent chemotherapy to work effectively at lower, less toxic doses.
3Reliability
If multiple B cell targeting strategies are combined with chemotherapy, then treatment effectiveness is improved, but therapy complexity increases
Solution Approach 1:
The patent merges B cell depletion therapy with immunogenic chemotherapy into a unified treatment protocol. By combining these two approaches sequentially (B cell depletion followed by chemotherapy), the patent achieves synergistic effects where the depletion removes immunosuppression and the chemotherapy induces immunogenic cell death, creating a more effective overall treatment than either approach alone.
Solution Approach 2:
The patent employs universal B cell depletion strategies (anti-CD19, anti-CD20 antibodies) that can be applied across different cancer types and can be combined with various immunogenic chemotherapeutic agents. This multi-functional approach allows the same depletion protocol to work with different chemotherapy regimens, simplifying the overall therapeutic framework despite the combination approach.
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 enhances the activation of cytotoxic T cells, leading to nearly complete tumor eradication by eliminating immunosuppressive B cells and sensitizing tumors to low-dose oxaliplatin, thereby improving treatment outcomes for prostate and liver cancers.
Implementation Method 1
one or more first composition that causes immunogenic cell death and/or of said epithelial cancer cells
Implementation Method 2
said second composition that reduces one or both of the number and function of said immunosuppressive B cells in said cancer comprises an antibody that specifically binds to said immunosuppressive B cells
Implementation Method 3
said second composition that reduces one or both of the number and function of said immunosuppressive B cells in said cancer comprises anti-PDL1 antibody
Data Source
AI summary
The invention provides a method for treating cancer in a subject in need thereof, wherein said subject comprises cancer tissue that ‘contains epithelial cancer cells and immunosuppressive 8 cells, and wherein said method comprises administering to said subject a therapeutically effective amount of a) one or more first composition that pauses—immunogenic eel’ death and/or of said epithelial cancer cells, and b) one or more second composition that reduces one or both of the number and function of said immunosuppressive B cells in said cancer.