CAR T Cell Targeting via Phospholipid Ether Complexes
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Solution Overview
Problem
Current CAR T cell therapies lack selectivity for specific tumor targets, leading to adverse side effects due to non-specific binding to normal tissues.
Innovation Solution
A complex comprising a chimeric antigen receptor (CAR) or T cell receptor (TCR) joined to a lipid with a target moiety, where the CAR is attached to the lipid through an interaction, allowing for selective binding to tumor cell membranes, utilizing various lipids and target moieties to enhance specificity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CAR T cell therapies are administered to treat cancer, then therapeutic efficacy is improved, but selectivity for tumor targets deteriorates leading to adverse side effects
Solution Approach 1:
The invention segments the targeting function by introducing a separate target moiety (such as a hapten or peptide tag) that is independently administered and localized to tumor cells. The CAR T cell targets this segmented marker rather than endogenous antigens, improving selectivity and reducing off-target effects while maintaining therapeutic efficacy.
Solution Approach 2:
The invention uses an intermediary target moiety (hapten or peptide tag) as a mediator between the CAR T cell and the tumor cell. This intermediary is specifically bound to tumor cells through antibodies or other binding agents, creating a selective bridge that directs CAR T cell activity precisely to tumor cells while sparing normal tissues.
2Power
If conventional CAR T cell therapies are used, then T cell effector functions are activated, but specificity for malignant cells deteriorates causing toxicity to normal tissues
Solution Approach 1:
The invention applies local quality by concentrating the target moiety specifically at tumor cell locations through localized administration of binding agents (antibodies, peptides). This creates a spatially differentiated environment where CAR T cells encounter high concentrations of target moieties only at tumor sites, enabling powerful effector function activation precisely where needed while avoiding activation against normal tissues.
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 selective targeting of tumor cells by CAR T cells, minimizing damage to normal tissues and improving the therapeutic efficacy while reducing adverse side effects.
Implementation Method 1
the lipid comprises a polar head group and a hydrophobic group. In some alternatives, the hydrophobic group is a carbon chain or a fatty acid such as an aliphatic chain
Implementation Method 2
In some alternatives, the lipid is a phospholipid ether. In some alternatives, the polar head comprises a choline, a phosphatidylcholine, sphingomyelin, phosphoethanolamine group
Data Source
AI summary
Aspects of the invention described herein relate to synthetic compounds that are useful for targeting and labeling tumor cells so as to facilitate recognition by binding agents including Chimeric Antigen Receptor T cells (CAR T cells), which are administered to a subject by intravenous or locoregional administration. Several compositions and methods of making and using these compositions to treat or inhibit a disease in a subject are contemplated.