Pre-emptive and therapeutic adoptive immunotherapy for nasopharyngeal carcinoma: Phenotype and effector function of T cells impact on clinical response. (1st February 2017)

• Record Type: Journal Article
• Authors: Smith, Corey; Lee, Victor; Schuessler, Andrea; Beagley, Leone; Rehan, Sweera; Tsang, Janice; Li, Vivian; Tiu, Randal; Smith, David; Neller, Michelle A.; Matthews, Katherine K.; Gostick, Emma; Price, David A.; Burrows, Jacqueline; Boyle, Glen M.; Chua, Daniel; Panizza, Benedict; Porceddu, Sandro V.; Nicholls, John; Kwong, Dora; Khanna, Rajiv
• Is Part Of: Oncoimmunology. Volume 6:Number 2(2017)
• Publication Date: 2017-02-01
• Subjects: Adoptive immunotherapy -- Epstein-Barr virus -- T cells -- safety -- nasopharyngeal carcinoma; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2016.1273311
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: 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.