Glycopeptide Composition Enhances T Cell Infiltration in Resistant Tumors
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Solution Overview
Problem
Cancer treatments, particularly for tumors resistant to immune checkpoint inhibitors, require enhancement to increase the efficacy of immune responses against cancer cells, as current therapies face challenges in overcoming resistance and improving patient outcomes.
Innovation Solution
Administration of a composition comprising glycopeptides obtained from gastrointestinal mucins with less than 25% free glycans, which enhances T cell expansion, infiltration, and activity, and modulates the immune microenvironment to increase anti-tumor responses by targeting tumor-specific antigens and reducing immune checkpoint molecules.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune checkpoint inhibitors are used to treat cancer, then the lifespan of some cancer patients is increased, but a number of cancers are resistant or can become resistant to these inhibitors
Solution Approach 1:
The patent introduces glycopeptide compositions as an intermediary substance that mediates between the immune checkpoint inhibitor and the tumor cells. These glycopeptides, derived from gastrointestinal mucins, serve as a bridge to enhance T cell activation and overcome resistance mechanisms, allowing the immune checkpoint inhibitor to effectively target resistant cancers by modulating the immune microenvironment
Solution Approach 2:
The invention employs a composite therapeutic approach by combining immune checkpoint inhibitors with glycopeptide compositions. This composite strategy integrates two different mechanisms of action: the checkpoint inhibition pathway and the glycopeptide-mediated T cell activation pathway, creating a synergistic effect that overcomes single-agent resistance while maintaining the core function of each component
2Reliability
If therapies are developed to enhance immune checkpoint inhibitor efficacy, then tumor sensitivity to therapy is increased, but the complexity of treatment regimens increases
Solution Approach 1:
The glycopeptide composition serves multiple functions simultaneously: it acts as an immune adjuvant to enhance T cell activation, functions as a microenvironment modulator to improve drug delivery, and serves as a resistance-overcoming agent. This multi-functionality allows a single therapeutic addition to address multiple aspects of treatment enhancement without proportionally increasing regimen complexity
Solution Approach 2:
The invention modifies key parameters of the immune response by introducing glycopeptides that change the activation threshold, cytokine profile, and T cell infiltration dynamics. These parameter changes enhance tumor sensitivity to checkpoint inhibitors while maintaining a manageable treatment complexity through standardized composition administration
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
The composition effectively increases the sensitivity of tumors to checkpoint-inhibitor therapy, reduces tumor weight and volume, and promotes a systemic immune response, potentially delaying or preventing tumor progression in subjects resistant to immune checkpoint inhibitors.
Implementation Method 1
instruct T cells to target antigens on the tumor cells using glycans on the glycopeptides as molecular mimicry of glycans on cancer cells
Implementation Method 2
bind and stimulate Toll-like Receptors (TLR) and initiate T-cell immunity by inducing maturation of DCs
Data Source
AI summary
Provided herein are methods and compositions for treating a tumor or increasing the anti-cancer effectiveness of an immune checkpoint inhibitor using glycopeptide containing compositions.