Abstract
In this study, we address one of the major critiques for tumor-infiltrating lymphocyte (TIL) therapythe time needed for proper expansion of a suitable product. We postulated that T-cell receptor activation in the first phase of expansion combined with an agonistic stimulation of CD137/4-1BB and interleukin-2 would favor preferential expansion of CD8+ TIL. Indeed, this novel 3-signal approach for optimal T-cell activation resulted in faster and more consistent expansion of CD8+CD3+ TIL. This new method allowed for successful expansion of TIL from cutaneous and uveal melanoma tumors in 100% of the cultures in 3 weeks. Finally, providing the 3 signals attributed to optimal T-cell activation led to expansion of TIL capable of recognizing their tumor counterpart in cutaneous and uveal melanoma. This new methodology for the initial phase of TIL expansion brings a new opportunity for translation of TIL therapy in challenging malignancies such as uveal melanoma.
Original language | English (US) |
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Pages (from-to) | 399-405 |
Number of pages | 7 |
Journal | Journal of Immunotherapy |
Volume | 41 |
Issue number | 9 |
DOIs | |
State | Published - Nov 1 2018 |
Keywords
- 4-1BB/CD137
- OKT3
- TIL
- cutaneous melanoma
- uveal melanoma
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Pharmacology
- Cancer Research