Genetically Engineered Erythrocytes for Targeted Anti-PD-1 Delivery
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Solution Overview
Problem
Current immunotherapy for cancer, particularly using anti-PD-1 monoclonal antibodies, faces challenges with non-targeted delivery to tumor tissues, low utilization efficiency, and higher systemic side effects due to autoimmunogenicity and nonspecific inflammation.
Innovation Solution
Genetically engineered erythrocytes carrying an anti-PD-1 single chain antibody are developed through a method involving lentiviral vector construction, packaging, and erythroid differentiation to achieve targeted delivery and enhanced T cell activation, reducing systemic side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-PD-1 monoclonal antibodies are used for immunotherapy, then therapeutic effect is achieved, but systemic side effects and autoimmunogenicity increase
Solution Approach 1:
Erythrocytes are used as intermediary carriers to deliver anti-PD-1 single chain antibodies to tumor tissues. The erythrocytes circulate in the bloodstream and naturally accumulate at tumor sites through the enhanced permeability and retention effect, thereby mediating the delivery of the therapeutic antibody and reducing systemic exposure and side effects.
Solution Approach 2:
The invention achieves localized delivery of the anti-PD-1 antibody to tumor tissues rather than systemic distribution. By conjugating the antibody to erythrocytes, the therapeutic agent is concentrated at the tumor site where erythrocytes naturally accumulate, creating local high concentration while maintaining low systemic levels.
2Reliability
If anti-PD-1 monoclonal antibodies are administered systemically, then immune response is activated, but utilization efficiency decreases due to non-targeted delivery
Solution Approach 1:
Erythrocytes serve as a natural delivery vehicle that accumulates at tumor sites, thereby mediating the targeted delivery of anti-PD-1 single chain antibodies to tumor tissues and improving the utilization efficiency of the immunotherapeutic agent.
Solution Approach 2:
The invention changes the delivery parameters by using erythrocytes as carriers, which alters the distribution pattern of the antibody from systemic to tumor-targeted. This parameter change in delivery localization significantly improves the utilization efficiency of the therapeutic agent.
3Reliability
If conventional immunotherapy is used, then cancer treatment is achieved, but tumor targeting capability is insufficient
Solution Approach 1:
Erythrocytes function as natural mediators that passively target tumor tissues through the enhanced permeability and retention effect. By conjugating anti-PD-1 single chain antibodies to erythrocytes, the system achieves improved tumor targeting capability while maintaining cancer treatment efficacy.
Data Source
AI summary
Provided are a method for preparing genetically engineered erythrocytes carrying an anti-PD-1 single chain antibody, and genetically engineered erythrocytes carrying the anti-PD-1 single chain antibody. The preparation method comprises the following steps: constructing a desired fragment sequence in a lentiviral expression vector, lentivirally packaging the vector of the desired sequence to obtain a high-titer lentiviral concentrate; isolating Lin−CD34− cells from peripheral blood mononuclear cells and enriching the Lin−CD34− cells; inducing the Lin−CD34− cells to differentiate into erythroid and performing proliferation thereon; using the lentiviral concentrate to infect the Lin−CD34− cells; and obtaining mature anti-PD-1 scFv erythrocytes via erythrocyte denucleation. The present genetically engineered erythrocytes carrying the anti-PD-1 single chain antibody can perform the targeted delivery of an anti-PD-1 single-chain antibody to tumor tissues.