Open Access
Table 3
Emerging directions in TIL therapy.
| Area | Description | Goal |
|---|---|---|
| Genetically engineered TILs | Incorporating CARs, TCRs, cytokines, or checkpoint knockouts (e.g., PD-1, CISH) to enhance tumor targeting and resistance to immunosuppression [20–22]. | Improve specificity, function, and durability of TILs. |
| Cytokine enhancement and on-demand support | Using IL-2 variants, IL-15, or engineered cytokine circuits (e.g., OBX-115) to boost TILs with reduced systemic toxicity [21, 70]. | Enhance in vivo expansion while minimizing toxicity. |
| Optimizing lymphodepletion regimens | Exploring reduced-intensity lymphodepletion to lower toxicity [72–74]; combining with immune checkpoint inhibitors (ICIs) for enhanced persistence [27]. | Reduce toxicity, broaden patient eligibility, and improve TIL engraftment. |
| Quality attributes for TIL products | Defining critical quality metrics: tumor-reactive T cells, cytolytic capacity, tissue-homing markers, persistence, and minimizing suppressive cells [29, 43, 77–79]. | Standardize product potency, ensure reproducibility, and improve clinical outcomes. |
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