Epstein-Barr virus (EBV)-specific immunotherapy in nasopharygneal carcinoma (NPC)

6025 Background: Immunotherapy for EBV-associated NPC is intriguing, as viral proteins serve as foreign tumor antigens for cytotoxic T cells (CTLs). EBV-specific CTLs are effective in PTLD, but translating this success to NPC is challenging. We conducted a feasibility study to establish the manufacture and administration of autologous EBV-specific CTLs and explore correlates of response. Methods: Eligibility criteria include incurable EBV+ NPC, ECOG PS ≤ 1, adequate end-organ function, and no chemotherapy within 2 weeks (wks). CTLs were generated using autologous EBV-transformed B cells to generate autologous EBV-specific CTLs. CTLs were administered in 2 infusions, 2 wks apart (2 X 107 and 1 X 108 cells/m2, respectively, for the 1st 3 patients, then 1 X 108 cells/m2 X 2 for remaining patients). Response was determined at 8 wks. Results: Ten patients were enrolled. CTLs were successfully generated in 9. Two patients came off study during CTL manufacture, due to decline in PS (n = 1) and tumor invasion into the brain (n = 1). One patient has a product available when clinically appropriate. There were no infusion-related events. Seven patients received CTLs. One had stable disease (SD) and remains progression-free at 64 wks, 4 had progressive disease and 2 await restaging. Five patients had EBV viral loads (VL) pre- and post-CTLs. VL remained undetectable in 1, decreased from 5300 to 1300 copies/ml in 1, increased from undetectable to 153 copies/ml in 1, and in 2 increased from 46,524 to 269,072 and 7,621 to 59,336 copies/ml, respectively. A CD3+/CD8+ phenotype predominated in the CTLs. LMP2- and EBNA-1 CTL specificity was evaluated by IFN-γ ELISPOTs. There were 2 responders to EBNA-1 (range: 100 to 150 sfc/106 cells), and 7 responders to LMP2 (range: 120 to 433 sfc/106 cells). Conclusions: EBV-specific CTLs can be generated from patients with NPC. CTLs are well-tolerated and may have some efficacy, as seen in 1 patient with SD. LMP2-specific CTLs were frequent, whereas EBNA-1-specificity was less common. While the sample size is small, the presence of LMP2 activity alone may not account for response. Factors critical to EBV-specific immunotherapy in NPC remain unclear. A phase II study to establish efficacy of this approach in less heavily pretreated NPC is underway. No significant financial relationships to disclose.