Abstract

Abstract Background: Until recently, treatment options for patients with head and neck cancer include a combination of surgery, chemotherapy and radiation. Although the combined use of these treatment options modestly improves survival, combination therapy increases toxicity. Overall survival of these treatment regimens for patients with advanced head and neck cancer is just over 10 months. Even with the newly approved and vastly more tolerable use of anti-PD-1 immunotherapy, survival is only extended by 3-5 months. In comparison, adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) has improved the median overall survival in patients with metastatic melanoma to 52 months. The goal of this study was to test the feasibility of expanding tumor-reactive TIL from head and neck tumors for the development of a clinical trial. Methods: Primary tumors were resected from 20 head and neck cancer patients. Tumors were minced into small fragments (1-3 mm3) and plated in high dose IL-2. After 4 weeks, expanded TIL were phenotyped by flow cytometry and tested for tumor reactivity by IFN-gamma production after co-culture of TIL with autologous tumor digest. IFN-gamma levels were determined by ELISA. Reactive TIL were expanded using a rapid expansion protocol (REP). Results: The mean expansion of TIL per fragment was 1.96 × 106. From 20 primary tumors, seven were contaminated and discarded. TIL were successfully expanded from 11/13 (85%) evaluable tumors. The phenotype of expanded TIL consisted of CD3− CD56+ NK cells and CD3+ T cells. Tumor-specific reactivity was analyzed for seven samples. TIL expanded from three (43%) tumors were predominantly CD8+ and were reactive against autologous tumor as determined by IFN-gamma ELISA. Expansion of TIL during REP resulted in an average 600-fold increase in cell numbers (range of 61 - 1,774 fold) and led to the depletion of NK cells and an increase of CD3+ T cells. Conclusions: In this study, we have demonstrated the feasibility of growing tumor-reactive TIL from head and neck tumors. This study raises the potential for the implementation of ACT with TIL for the treatment of head and neck cancer patients. Citation Format: Luz Nagle, Amy Mackay Weber, MacLean Hall, Matthew Beatty, J. Trad Wadsworth, Caitlin McMullen, Krupal Patel, Kathryn Vorwald, Christine Chung, Shari Pilon-Thomas. Expansion of tumor-specific tumor-infiltrating lymphocytes (TIL) from head and neck tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2178.

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