biostudies-literatureTavera RJNCI NIH HHS399-405https://www.ebi.ac.uk/biostudies/studies/S-EPMC6177302biostudies-literatureUnknown41(9)In this study, we address one of the major critiques for tumor-infiltrating lymphocyte (TIL) therapy-the 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 CD8CD3 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. Journal of immunotherapy (Hagerstown, Md. : 1997)Utilizing T-cell Activation Signals 1, 2, and 3 for Tumor-infiltrating Lymphocytes (TIL) Expansion: The Advantage Over the Sole Use of Interleukin-2 in Cutaneous and Uveal Melanoma.PMC6177302P30 CA016672Forget MAHaymaker CRamachandran RFulbright OJBernatchez CFlores ESakellariou-Thompson DThorsen STWahl ABhatta AGonzalez AMKim YUHwu PMansaray RCreasy CAToth CRadvanyi LGWardell SGombos DSPatel SPAmaria RNTavera RJfalseUtilizing T-cell Activation Signals 1, 2, and 3 for Tumor-infiltrating Lymphocytes (TIL) Expansion: The Advantage Over the Sole Use of Interleukin-2 in Cutaneous and Uveal Melanoma.In this study, we address one of the major critiques for tumor-infiltrating lymphocyte (TIL) therapy-the 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 CD8CD3 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. 2018-01-01T00:00:00Z2018 Nov/Dec2026-05-03T19:06:41.153Z2019-11-07T08:01:04ZS-EPMC61773022975788910.1097/cji.000000000000023010.1097/CJI.0000000000000230