Tumor-Infiltrating Lymphocyte Selection for Melanoma Reactivity
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Solution Overview
Problem
Current methods for treating melanoma are inadequate in eliciting a robust anti-tumor immune response, as existing tumor-infiltrating lymphocytes (TILs) do not effectively target melanoma cells.
Innovation Solution
Producing TILs with enhanced tumor reactivity by selecting donor melanoma cells expressing a specific gene signature of 12 chemokines (CCL2, CCL3, CCL4, CCL5, CCL8, CCL18, CCL19, CCL21, CXCL9, CXCL10, CXCL11, CXCL13) and using them in therapeutic compositions to enhance anti-tumor immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional TILs are used for melanoma treatment, then the treatment can be administered, but the anti-tumor immune response is not robust
Solution Approach 1:
The patent applies parameter changes by selecting and expanding TILs based on specific phenotypic markers (CXCR3+, PD-1+, TIM-3+) and chemokine receptor expression patterns. This selective parameter-based identification and expansion of TIL subsets with enhanced tumor-homing capability transforms the conventional TIL approach into a more effective therapy with robust anti-tumor immune responses
2Ease of manufacture
If TILs are expanded without selection criteria, then the production process is simpler, but the tumor reactivity is insufficient
Solution Approach 1:
The patent applies local quality by identifying and isolating specific subsets of TILs with particular phenotypic characteristics (CXCR3+, PD-1+, TIM-3+ expression) and chemokine receptor profiles (CXCR1, CXCR2, CXCR3, CCR1, CCR2, CCR5). This localized selection of TILs with enhanced tumor-homing properties within the broader TIL population achieves superior tumor reactivity while maintaining a manageable production process
Data Source
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AI summary
Disclosed are compositions and methods for targeted treatment of infections and cancers expressing cancers. In particular, tumor infiltrating lymphocytes (TILs) are identified that can be used with adoptive cell transfer to target, penetrate, and kill solid tumor masses. Therefore, also disclosed are methods of providing an immunotherapy in a subject with an infection or cancer that involves adoptive transfer of the disclosed TILs.