Autologous T Cell Isolation via Mutated p53 APC Pulsing
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Solution Overview
Problem
Current methods for adoptive cell therapy (ACT) face challenges in identifying and isolating T cells that specifically recognize cancer antigens, particularly those with mutated human p53 amino acid sequences.
Innovation Solution
A method is developed to isolate T cells with antigenic specificity for mutated human p53 amino acid sequences by inducing autologous antigen-presenting cells (APCs) to present these sequences. This is achieved through pulsing APCs with peptides or introducing nucleotide sequences encoding the mutated p53 sequences, followed by co-culturing with autologous T cells and selecting those with antigenic specificity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional methods are used to identify and isolate T cells specific to cancer antigens, then the process is time-consuming and inefficient, but T cells with antigenic specificity can be obtained
Solution Approach 1:
The patent applies preliminary action by pre-pulsing antigen-presenting cells with mutated p53 peptides before co-culturing with T cells. This preparatory step enriches the APC population with the specific antigen of interest, allowing for more efficient and faster isolation of antigen-specific T cells compared to conventional screening methods
Solution Approach 2:
The patent uses mutated p53 peptides as an intermediary substance to bridge the interaction between APCs and T cells. By introducing these specific peptide antigens, the system enables selective enrichment of T cells that recognize the mutated p53 sequence, improving both the speed and efficiency of isolation
2Measurement precision
If autologous APCs are induced to present mutated p53 sequences through peptide pulsing or nucleotide introduction, then T cells with high antigenic specificity can be isolated, but the procedure complexity increases
Solution Approach 1:
The patent segments the complex isolation process into distinct modular steps: (1) APC isolation and pulsing with mutated p53 peptides or nucleotides, (2) co-culturing with patient T cells, and (3) selection of antigen-specific T cells. This segmentation makes the complex procedure more manageable and reproducible while maintaining high specificity
Solution Approach 2:
The patent changes key parameters of the APCs by introducing mutated p53 peptides or nucleotide sequences, thereby modifying their antigen-presenting capabilities. This parameter change enables the APCs to specifically present the mutated antigen, allowing for precise isolation of T cells with high antigenic specificity
Data Source
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AI summary
Disclosed are methods of isolating T cells having antigenic specificity for a mutated p53 amino acid sequence encoded by a cancer-specific p53 mutation, the method comprising: inducing autologous APCs of the patient to present the mutated p53 amino acid sequence; co-culturing autologous T cells of the patient with the autologous APCs that present the mutated p53 amino acid sequence; and selecting the autologous T cells. Also disclosed are related methods of preparing a population of cells, populations of cells, pharmaceutical compositions, and methods of treating or preventing cancer.