Prospects for a personalized peptide vaccine against lung cancer

ABSTRACT

Introduction: The tumor characteristics and immunological status of the host should be carefully considered for the successful development of cancer peptide vaccines. Recently, personalized peptide vaccines (PPV) that individually select antigens for each patient are being developed for lung cancer.

Areas covered: Novel PPV, in which appropriate vaccine antigens are selected in each patient by assessing preexisting immunity to a panel of vaccine peptide candidates, have been attempted with promising results in early-phase clinical trials for lung cancer. Additionally, PPV targeting neo-antigens derived from genetic mutations have been currently attempted with high anticipation of success in various cancers, because they can be recognized as foreign by the host immune system. In this review, we present an overview of the current progress and future directions of such PPV for patients with lung cancer.

Expert opinion: Both genetic characterization of tumor cells and assessment of the immune responses to potential tumor antigens might be a key component for facilitating successful cancer vaccine development. In addition, not only selection of immunogenic epitopes, but also appropriate modulation of the host immunological status should be considered; clinical trials combining neo-antigen vaccines and anti-PD-1 antibodies for lung cancer are currently ongoing and their results are awaited.

KEYWORDS:

• Cancer immunotherapy
• clinical trial
• immune checkpoint inhibitor
• lung cancer
• mutation
• neo-antigen
• personalized peptide vaccine

Article highlights

• Anti-tumor immunity may depend on both tumor tissue characteristics and host immunological status.

• A novel PPV was developed, in which appropriate vaccine antigens with immunological memory are selected in each patient by assessing preexisting immunity to a panel of vaccine peptide candidates.

• Neo-antigens derived from genetic mutations might be highly immunogenic and efficiently induce antigen-specific T cells with high avidity, because they are recognized as ‘non-self’ or foreign by the immune system.

• Early phase clinical trials of personalized cancer vaccines targeting neo-antigens have been initiated against various cancers, and some of them have recently been reported with promising results.

• Combination therapies with peptide-based cancer vaccines including neo-antigen-derived peptides and immune modulators are expected to show better clinical outcomes; clinical trials combining neo-epitope vaccines and anti-PD-1 antibodies for patients with NSCLC are currently ongoing and their results are awaited.

• Since not all patients showed clinical benefits from PPV, predictive biomarkers for patient selection remain to be identified to improve the efficacy of PPV.

Declaration of interest

T Sasada has received grants from Taiho Pharmaceutical Co. Ltd and BrightPath Biotherapeutics Co., Ltd. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was funded by grants from JSPS KAKENHI [17H04278] and AMED [18ck0106360h0002].