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

Rene J. Tavera, Marie Andree Forget, Young Uk Kim, Donastas Sakellariou-Thompson, Caitlin A. Creasy, Ankit Bhatta, Orenthial J. Fulbright, Renjith Ramachandran, Shawne T. Thorsen, Esteban Flores, Arely Wahl, Audrey M. Gonzalez, Christopher Toth, Seth Wardell, Rahmatu Mansaray, Laszlo G. Radvanyi, Dan S. Gombos, Sapna P. Patel, Patrick Hwu, Rodabe N. AmariaChantale Bernatchez, Cara Haymaker

Research output: Contribution to journalArticle

12 Scopus citations

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 languageEnglish (US)
Pages (from-to)399-405
Number of pages7
JournalJournal of Immunotherapy
Volume41
Issue number9
DOIs
StatePublished - Nov 1 2018

Keywords

  • 4-1BB/CD137
  • OKT3
  • TIL
  • cutaneous melanoma
  • uveal melanoma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

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