Amplicon Surface Antigen Selection for Solid Tumor CAR-T Targeting
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Solution Overview
Problem
Current immune-oncology therapies for solid tumors lack stable and highly expressed cell surface proteins that are specific to malignant cells, limiting the effectiveness of CAR-T cell therapy and related approaches.
Innovation Solution
Identify clonally and chromosomally integrated amplicons that co-amplify essential oncogenes with cell surface proteins using genomic profiling techniques like short read whole genome sequencing, RNA-Seq, and long read WGS, to predict personalized surface antigens for targeted therapies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional immune-oncology therapies are used for solid tumors, then treatment approaches can be applied, but the lack of stable and highly expressed cell surface proteins limits effectiveness
Solution Approach 1:
The patent performs preliminary identification of candidate cell surface proteins through genomic sequencing and amplicon detection before initiating CAR-T cell therapy. This allows selection of optimal targets based on tumor-specific genetic alterations, ensuring the therapy is directed against proteins that are stably and highly expressed in the patient's tumor cells.
Solution Approach 2:
The patent changes the selection criteria for target proteins from conventional markers to tumor-specific proteins identified through genomic alterations. By detecting amplicons containing cell surface proteins co-amplified with oncogenes, the method identifies proteins with higher expression levels and tumor specificity, thereby improving therapeutic effectiveness.
2Adaptability or versatility
If cell surface proteins are targeted that are not specifically expressed in malignant cells, then broader applicability is achieved, but specificity to malignant cells decreases
Solution Approach 1:
The patent applies local quality by identifying cell surface proteins that are specifically over-expressed in malignant cells due to tumor-specific genomic alterations. Each patient's tumor is analyzed for unique amplicons containing cell surface proteins, creating a personalized target list that is specific to that patient's cancer cells while maintaining versatility across different cancer types.
Solution Approach 2:
The patent segments the genome into specific amplicon regions containing cell surface protein genes that are co-amplified with oncogenes. By focusing on these discrete genomic segments rather than whole-genome expression profiles, the method identifies proteins with high tumor-specificity while maintaining broad applicability across different cancer types.
3Measurement precision
If genomic profiling techniques are used to identify personalized targets, then treatment precision is improved, but diagnostic complexity increases
Solution Approach 1:
The patent extracts specific information from complex genomic data by focusing only on amplicons containing cell surface protein genes that are co-amplified with oncogenes. Rather than analyzing the entire genome, the method isolates and analyzes only the relevant genomic segments, simplifying the diagnostic process while maintaining high precision in target identification.
Data Source
AI summary
Methods for identifying oncogene amplicon-encoded cell surface proteins in a subject and preparing adoptive immunotherapies directed to cell surface proteins.