Immune Checkpoint Composition for PD-L1 Suppression and T-Cell Killing
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Solution Overview
Problem
Existing anti-PD-1/PD-L1 antibody immunotherapy for cancer treatment has significant side effects and limited benefits due to the expression of PD-L1 in tumor cells, inhibiting T cell activation and killing of tumor cells.
Innovation Solution
A novel anti-tumor pharmaceutical composition comprising cannabidiol, paroxetine hydrochloride, and a T-cell enhancer such as vitamin E or thymosin, which inhibits PD-L1 expression on tumor cells, enhancing T cell activity and killing capacity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-PD-1/PD-L1 antibody immunotherapy is used, then tumor treatment benefit is improved, but side effects increase
Solution Approach 1:
The patent changes the mechanism of action from antibody-based immune checkpoint blockade to small molecule compounds (cannabidiol and paroxetine hydrochloride) that directly inhibit PD-L1 expression. This parameter change in therapeutic approach reduces side effects while maintaining anti-tumor efficacy through a different molecular mechanism that avoids the harmful effects of traditional antibody therapy.
Solution Approach 2:
The patent combines cannabidiol and paroxetine hydrochloride into a composite pharmaceutical composition that synergistically inhibits PD-L1 expression. This composite approach enhances anti-tumor effects while reducing side effects compared to single-agent therapy, addressing both the benefit and harmful effect dimensions of the contradiction.
2Reliability
If PD-L1 expression is high in tumor cells, then anti-PD-1/PD-L1 therapy response is improved, but T cell activation is inhibited
Solution Approach 1:
The patent extracts and directly targets the PD-L1 protein expression on tumor cells using small molecule inhibitors that specifically reduce PD-L1 levels. By removing the harmful PD-L1 expression directly rather than blocking its interaction, the therapy eliminates the inhibition of T cell activation while maintaining response in PD-L1 high expression tumors.
Solution Approach 2:
The patent introduces cannabidiol and paroxetine hydrochloride as intermediary substances that mediate between the tumor cell's PD-L1 expression and T cell activation. These small molecules act as intermediaries that suppress PD-L1 expression, thereby removing the barrier to T cell activation without requiring direct T cell engagement.
Data Source
AI summary
Disclosed herein is an anti-tumor pharmaceutical composition based on immune checkpoint blockade and use thereof. The anti-tumor pharmaceutical composition comprises: paroxetine hydrochloride, and a T-cell enhancer, wherein the T-cell enhancer is at least one of vitamin E and thymosin. Through a series of in vitro and in vivo experiments, cannabidiol and paroxetine hydrochloride were first found to be capable of effectively reducing the expression of PD-L1 on the tumor cell membrane, thereby blocking the PD-1/PD-L1 signaling pathway and enhancing the ability of T cells to kill tumor cells. The T-cell enhancer added on this basis can further increase the quantity and activity of T cells, significantly increase the killing ability of T cells after immunosuppression is relieved, and greatly improve the anti-tumor effect of the drug. The components of the pharmaceutical composition used in the present invention, namely, cannabidiol, paroxetine hydrochloride, and vitamin E+thymosin, can exert a synergistic effect and improve the anti-tumor effect.