Engineered Stem Cells for Targeted Cancer Therapy
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current cancer treatments using checkpoint immunotherapy, such as PD-1/PD-L1 pathway interaction, have limited efficacy in 70% of patients and can cause autoimmune responses, necessitating improved tumor-targeting therapies that selectively accumulate in tumors without harming normal tissues.
Innovation Solution
Engineered stem cells, including umbilical cord mesenchymal stem cells, are genetically modified with a suicide gene (e.g., thymidine kinase) and immune checkpoint genes (e.g., PD-1) along with a natural cytotoxicity triggering receptor (NCR3), to enhance tumor targeting and immune response while minimizing side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If checkpoint immunotherapy (PD-1/PD-L1 pathway) is used to treat cancer, then immune response against tumor is enhanced, but autoimmune responses in peripheral normal tissue occur and treatment efficacy is limited in 70% of patients
Solution Approach 1:
The patent applies local quality by engineering stem cells to selectively accumulate checkpoint inhibitors only within the tumor microenvironment through tumor-specific homing receptors (such as integrins or chemokine receptors that recognize tumor-associated signals). This ensures the immunotherapeutic effect is localized to cancer tissue while peripheral normal tissues remain unaffected, resolving the contradiction between enhancing anti-tumor immunity and avoiding autoimmune responses
Solution Approach 2:
The patent uses engineered stem cells as an intermediary vehicle to deliver checkpoint inhibitors directly to tumors. These stem cells are modified with tumor-homing capabilities and serve as living carriers that selectively transport the therapeutic agents to the target site, thereby mediating between the immunotherapeutic goal and the need for selective tumor targeting without systemic side effects
2Reliability
If checkpoint inhibitors are administered systemically to enhance immune response, then tumor-specific T-cell responses are increased, but the inhibitors accumulate in peripheral normal tissue causing autoimmune complications
Solution Approach 1:
The patent implements local quality by equipping stem cells with tumor-specific targeting moieties (such as antibodies or ligands that bind to tumor-associated antigens or overexpressed receptors on cancer cells). This enables the stem cells to selectively accumulate checkpoint inhibitors at the tumor site while avoiding peripheral normal tissues, thus enhancing immune response locally without causing systemic autoimmune complications
Solution Approach 2:
The patent applies self-service by engineering stem cells with autonomous tumor-homing capabilities through expression of specific receptors or ligands that naturally guide them to tumor sites. These modified stem cells self-direct to tumors without external guidance, automatically delivering checkpoint inhibitors precisely where needed while sparing healthy tissues from exposure
Data Source
AI summary
The present disclosure provides an engineered stem cell, comprising a vector comprising a polynucleotide comprising a nucleic acid sequence of suicide gene, a nucleic acid sequence of immune checkpoint gene and a natural cytotoxicity triggering receptor or a TNF-related apoptosis-inducing ligand, wherein the stem cell is a tumor-targeting cell. The present disclosure also provides a method for treating a cancer or enhancing intratumor immunity or enhancing immunity in tumor microenvironment in a subject, comprising administering an effective amount of the engineered stem cell of the present disclosure to the subject.