Immunotherapeutic approaches in nasopharyngeal carcinoma

ABSTRACT

Introduction: Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia. Epstein-Barr virus (EBV) represents a unique etiological culprit in the poorly differentiated nonkeratinizing and undifferentiated subtypes. EBV antigens are expressed on tumor cells albeit in a restricted manner. Treatment options for recurrent or metastatic disease are limited. Nevertheless, emerging data from immunotherapy studies in NPC have shed light into their potential antitumor efficacy.

Areas covered: This article reviews existing clinical evidence for different immunotherapeutic approaches for NPC, including adoptive cellular therapy, therapeutic cancer vaccines, and immune checkpoint inhibitors.

Expert opinion: There is a growing understanding on EBV virology and the immune evasion mechanisms in NPC. Immunotherapeutic strategies leveraging these properties have shown encouraging efficacy and safety results in early-phase clinical studies. Moving forward, areas to be addressed include appropriate patient selection, optimal incorporation into standard treatment paradigms, biomarker identification, as well as the development of scalable and reproducible immune product generation processes.

KEYWORDS:

• Adoptive cell therapy
• cancer vaccine
• Epstein-Barr virus (EBV)
• immunotherapy
• monoclonal antibody
• nasopharyngeal carcinoma (NPC)

Article highlights

• Nasopharyngeal carcinoma exhibits restricted EBV antigens expression, which are potential therapeutic targets for immune modulation.

• An immunosuppressive milieu is present in NPC which facilitates tumor persistence and progression.

• Adoptive autologous cytotoxic T-cell therapy and therapeutic cancer vaccines have shown early success in inducing tumor responses in a small subset of treatment-refractory patients.

• Phase I/II single-arm studies have confirmed the efficacy and safety of three anti-PD-1 immune checkpoint inhibitors: pembrolizumab, nivolumab, and camrelizumab, in recurrent or metastatic NPC.

• Future research directions include technical refinement, exploration of the combinatorial approach with chemo-/radiotherapy and biomarker identification.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

One of the peer reviewers on this manuscript receives research support from and has a consultancy agreement with Tessa Therapeutics, which is performing a phase 3 clinical trial of T-cell therapy for NPC in Singapore. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper is not funded.