P2RY2 Activity Modulators for B7-H3-Linked T Cell Immunotherapy
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Solution Overview
Problem
Current cancer immunotherapies, such as CAR-T and immune checkpoint blocking therapies, are only effective in some patients, and there is a need for improved treatments that can enhance the activity of immune cells to combat various cancer types, particularly those with lower responses to CTLA-4 and PD-1/PD-L1 pathway blockade.
Innovation Solution
The use of P2Y purinoceptor 2 (P2RY2) activity modulators in T cell immunotherapy, including P2RY2-specific activity decreasing compounds, to modulate immune cell function and enhance cancer treatment efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current cancer immunotherapies (CAR-T and immune checkpoint blocking therapies) are used, then T cell activity is enhanced to combat cancer, but treatment effectiveness is limited to only some patients
Solution Approach 1:
The patent changes the molecular target parameter from conventional checkpoints (PD-1/PD-L1, CTLA-4) to P2RY2 receptor on tumor cells. This parameter change enables the therapy to work through a different mechanism (purinergic signaling modulation) that may be effective in patients who do not respond to conventional immunotherapies, thereby improving both reliability and adaptability
Solution Approach 2:
The patent introduces P2RY2 modulators as intermediary molecules that bind to P2RY2 receptors on tumor cells. These modulators act as mediators to block purinergic signaling pathways that suppress T cell function, thereby enhancing T cell anti-cancer activity without directly modifying T cells or using conventional checkpoint blockers
2Productivity
If P2RY2 activity modulators are used to enhance T cell anti-cancer activity, then cancer treatment efficacy is improved, but the mechanism of action and target specificity must be precisely controlled
Solution Approach 1:
The patent applies local quality by targeting P2RY2 receptors specifically on tumor cells rather than systemically modulating all purinergic signaling. This localized targeting approach enhances treatment efficacy at the tumor site while minimizing off-target effects, thereby improving both productivity and target specificity
Solution Approach 2:
The patent replaces the mechanical/cellular approach of CAR-T cell engineering with a pharmacological approach using small molecule P2RY2 modulators. This substitution simplifies the treatment mechanism while maintaining target specificity through high-affinity binding of modulators to P2RY2 receptors, improving both efficacy and precision
Data Source
AI summary
The present invention relates to a P2Y purinoceptor 2 (P2RY2) activity modulator for use in T cell immunotherapy. The present invention further relates to a polynucleotide encoding a P2RY2 activity modulator and to a host cell comprising the P2RY2 activity modulator for use in T cell immunotherapy. Furthermore, the present invention relates to a method of identifying 5 a subject amenable to T cell immunotherapy comprising (A) determining in a sample of said subject the activity of P2RY2; (B) comparing the activity determined in step (A) to a reference; and identifying a subject amenable to T cell immunotherapy based on the comparison of step (B), as well as to a method for identifying a P2RY2 activity modulator, said method comprising (I) contacting a host cell with a candidate compound suspected to be a P2RY2 activity 10 modulator; (II) determining B7-H3 activity in said host cell; (III) comparing the B7-H3 activity determined in step (II) to a control; and (IV) identifying a P2RY2 activity modulator based on the comparison in step (III).