Pre-emptive and therapeutic adoptive immunotherapy for nasopharyngeal carcinoma: Phenotype and effector function of T cells impact on clinical response

• Main Authors: Corey Smith, Victor Lee, Andrea Schuessler, Leone Beagley, Sweera Rehan, Janice Tsang, Vivian Li, Randal Tiu, David Smith, Michelle A. Neller, Katherine K. Matthews, Emma Gostick, David A. Price, Jacqueline Burrows, Glen M. Boyle, Daniel Chua, Benedict Panizza, Sandro V. Porceddu, John Nicholls, Dora Kwong, Rajiv Khanna
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2017-02-01
• Series: OncoImmunology
• Subjects: adoptive immunotherapy; epstein-barr virus; t cells; safety; nasopharyngeal carcinoma
• Online Access: http://dx.doi.org/10.1080/2162402X.2016.1273311

Adoptive T cell therapy has emerged as a powerful strategy to treat human cancers especially haematological malignancies. Extension of these therapies to solid cancers remains a significant challenge especially in the context of defining immunological correlates of clinical responses. Here we describe results from a clinical study investigating autologous Epstein-Barr virus (EBV)-specific T cells generated using a novel AdE1-LMPpoly vector to treat patients with nasopharyngeal carcinoma (NPC) either pre-emptively in at-risk patients with no or minimal residual disease (N/MRD) or therapeutically in patients with active recurrent/metastatic disease (ARMD). Tolerability, safety and efficacy, including progression-free survival (PFS) and overall survival (OS), were evaluated following adoptive T-cell immunotherapy. Twenty-nine patients, including 20 with ARMD and nine with N/MRD, successfully completed T-cell therapy. After a median follow-up of 18.5 months, the median PFS was 5.5 months (95% CI 2.1 to 9.0 months) and the median OS was 38.1 months (95% CI 17.2 months to not reached). Post-immunotherapy analyses revealed that disease stabilization in ARMD patients was significantly associated with the functional and phenotypic composition of in vitro-expanded T cell immunotherapy. These included a higher proportion of effector CD8+ T-cells and an increased number of EBV-specific T-cells with broader antigen specificity. These observations indicate that adoptive immunotherapy with AdE1-LMPpoly-expanded T cells stabilizes relapsed, refractory NPC without significant toxicity. Promising clinical outcomes in N/MRD patients further suggest a potential role for this approach as a consolidation treatment following first-line chemotherapy.