31O - T cell therapy with EBV-specific cytotoxic T-lymphocytes for patients with nasopharyngeal carcinoma

Date 14 December 2018
Event ESMO Immuno-Oncology Congress 2018
Session Proffered Paper session II
Topics Head and Neck Cancers
Presenter Patrizia Comoli
Citation Annals of Oncology (2018) 29 (suppl_10): x11-x16. 10.1093/annonc/mdy485
Authors P. Pedrazzoli1, P. Comoli2, S. Secondino1, A. Gurrado2, A. Pagani1, M. Zecca3
  • 1Oncology Departement, Fondazione IRCCS Policlinico San Matteo, 27100 - Pavia/IT
  • 2Cell Factory, Fondazione IRCCS Policlinico San Matteo, 27100 - Pavia/IT
  • 3Pediatric Oncology, Fondazione IRCCS Policlinico San Matteo, 27100 - Pavia/IT

Abstract

Background

 Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-related, highly chemo-radiosensitive malignancy. However, one-third of patients are considered to be incurable because of metastatic or recurrence disease. Expression of antigenic viral proteins by malignant cells constitutes a good target for immunotherapeutic strategies. Although the majority of clinical data have been obtained in the setting of EBV-related posttransplant lymphoproliferative disorders, this therapeutic approach has been more recently applied to solid tumors.

Methods

We and others have implemented T-cell therapy programs for patients with NPC failing conventional treatment. The feasibility of expanding EBV-targeted cytotoxic T lymphocytes (CTL) by stimulation with EBV-transformed lymphoblastoid cell lines (LCLs) has been demonstrated, and clinical trials were conducted, based on administration of 2 or more doses of EBV-CTLs (4-40 x 107/dose), supported by in vivo rhIL-2 infusion and, in some cases, pre-treatment with lymphodepleting chemo or immunotherapy.

Results

So far, more than 60 patients were treated in different centers for refractory/relapsed advanced NPC, and about 20% objective responses, including some complete responses, were observed, with no or limited adverse events. These results are encouraging, although further improvements to the laboratory and clinical protocols are clearly necessary to increase anti-cancer activity. One approach that our center has lately pursued is to test the efficacy of CTL therapy in earlier stages of disease, in particular immediately after first line chemotherapy for relapsed disease. The clinical results of this attempt seem to improve overall survival as compared with conventional therapies, and justify a prospective trial in this specific setting.

Conclusions

EBV-specific CTL therapy is safe and associated with clinical benefit in patients with refractory or metastatic NPC. Sequential combination of CTL therapy with other agents, such as checkpoint inhibitors, could yield optimal results.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Paolo Pedrazzoli.

Funding

Fondazione IRCCS Policlinico San Matteo.

Disclosure

All authors have declared no conflicts of interest.