Phospholipid Adjuvant for TADC Maturation in Tumor Immunity
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Solution Overview
Problem
Dendritic cells in the tumor microenvironment, known as tumor-associated dendritic cells (TADC), exhibit immunosuppressive properties, leading to reduced anti-tumor activity and potential immune tolerance, hindering effective cancer immunotherapy.
Innovation Solution
Administration of a composition comprising phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS) to immature dendritic cells, inducing their maturation into mature bone marrow-derived dendritic cells (BMDCs) and enhancing inflammatory cytokine production.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If dendritic cells are present in tumor microenvironment, then antigen presentation capability is provided, but immunosuppressive activity increases and anti-tumor immune response is reduced
Solution Approach 1:
The patent applies parameter changes by modifying the functional state of dendritic cells through specific chemical compounds (e.g., epigallocatechin gallate, quercetin, resveratrol) that induce maturation of immature dendritic cells into mature dendritic cells. This transformation changes key parameters including increased expression of MHC class II molecules, increased costimulatory molecules (CD80, CD86), and altered cytokine production profiles, thereby converting immunosuppressive cells into immunostimulatory cells
Solution Approach 2:
The patent converts the harmful immunosuppressive function of tumor-associated dendritic cells into a beneficial anti-tumor immune response. By administering specific compounds that induce dendritic cell maturation, the patent transforms cells that were previously suppressing immune activity into cells that actively stimulate anti-tumor immunity through enhanced antigen presentation and cytokine production
2Productivity
If conventional cancer immunotherapy is used, then treatment is administered, but anti-tumor activity is reduced due to dysfunctional dendritic cells
Solution Approach 1:
The patent applies preliminary action by administering compounds that mature dendritic cells before they can exert their immunosuppressive effects in the tumor microenvironment. The maturation process is induced in advance through exposure to specific chemicals, preparing the dendritic cells to function properly before they encounter tumor antigens, thereby enhancing the effectiveness of subsequent immune responses
3Manufacturing precision
If dendritic cells mature in tumor microenvironment, then costimulatory molecule expression increases, but this naturally does not occur and requires external induction
Solution Approach 1:
The patent applies self-service by utilizing naturally occurring compounds (such as epigallocatechin gallate from green tea, quercetin from onions and apples, and resveratrol from grapes) that can induce dendritic cell maturation through their inherent biological activities. These compounds trigger signaling pathways that lead to spontaneous maturation of dendritic cells without requiring complex external intervention or sophisticated delivery systems
Data Source
AI summary
The present invention aims to provide means to maintain and enhance the anti-tumor activity of TADC in a tumor microenvironment. The present inventors found that when a composition comprising three kinds of phospholipids “cPLs adjuvant” is administered, the degree of growth of tumors implanted to mice was notably suppressed, and confirmed that immature dendritic cells, when cultured in vitro in the presence of the cPLs adjuvant, become mature bone marrow-derived dendritic cells and induce cytokine production.