Abstract CT136: Therapeutic and prophylactic AdE1-LMPpoly-based adoptive T-cell immunotherapy for Epstein-Barr virus-associated nasopharyngeal carcinoma
Authors: Smith Corey , Schuessler Andrea , Tsang Janice , Beagley Leone , Lee Victor , Panizza Ben , Porceddu Sandro , Nicholls John , Kwong Dora , Khanna Rajiv 
Published: July 2016

Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is endemic in regions of South-East Asia, with incidence as high as 25-50 cases per 100,000 people in southern China. While current standard therapy is curative for a subset with stage I or II disease, a high proportion of patients relapse and many patients are still initially diagnosed with advanced stage III or IV disease, where overall 5-year survival is significantly reduced. EBV-specific immunotherapy has been successfully used in the treatment of post-transplant lymphomas and may have the potential application to improve outcomes in NPC patients. We have designed the AdE1-LMPpoly vector to promote rapid expansion of CD8+ T cells specific for the latent membrane proteins (LMP) 1&2 and EBV nuclear antigen 1 (EBNA1) expressed in NPC. We recruited a total of 52 NPC patients, including 42 patients with refractory stage IV NPC disease and 11 at-risk patients with no or minimal residual disease (referred to as N/MRD patients). Of these, 6 patients with refractory disease were withdrawn prior to the commencement of T cell manufacture. Using AdE1-LMpoly, we successfully expanded autologous EBV-specific T cells from 35 NPC patients, while 11 patients showed no or minimal expansion of antigen-specific T cells. Thirty patients, including 21 patients with active disease and nine N/MRD patients, successfully completed autologous T cell therapy defined by the administration of at least two cycles of immunotherapy. None of these patients showed treatment-related grade 3, 4, or 5 adverse events as per the NCI Common Terminology Criteria for Adverse Events. The time to progression in patients with refractory stage IV NPC disease ranged from 6 to 456 days from the time of first T cell infusion, with a median time to progression of 63 days, while median progression-free survival in N/MRD patients was 527 days. Refractory patients showed a median survival of 478 days following recruitment, while all N/MRD patients remain alive. The median overall survival for a corresponding refractory stage IV disease cohort during the study period from the same institute was 309 days. Our study suggests that autologous EBV-specific T cells are a safe novel treatment option for NPC patients, and may offer better clinical benefit for patients, particularly when T cell therapy is administered during the early stages of the disease.

Citation Format: Corey Smith, Andrea Schuessler, Janice Tsang, Leone Beagley, Victor Lee, Ben Panizza, Sandro Porceddu, John Nicholls, Dora Kwong, Rajiv Khanna. Therapeutic and prophylactic AdE1-LMPpoly-based adoptive T-cell immunotherapy for Epstein-Barr virus-associated nasopharyngeal carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT136.