Personalized neoantigen vaccines: a glimmer of hope for glioblastoma

ABSTRACT

Introduction

Glioblastoma multiforme (GBM) is the most prevalent primary brain tumor. In spite of the rigorous multimodal treatment involving surgery and radiochemotherapy, GBM has a dismal prognosis and rapid relapsing potential. Hence, search for novel therapeutic agents still continues. Neoantigens are the tumor-specific antigens which arise due to somatic mutations in the tumor genome. In recent years, personalized vaccine approach targeting neoantigens has been explored widely in cancer immunotherapy and several efforts have also been made to revolutionize the immunotherapy of cold tumors such as GBM using neoantigen targeted vaccines.

Areas covered

In this review, we discuss the clinical application of personalized neoantigen targeted vaccine strategy in GBM immunotherapy. While discussing this strategy, we brief about the current challenges faced in GBM treatment by the novel immunotherapeutics.

Expert opinion

To date, very few vaccines developed for GBM have reached till phase III clinical development. Early-phase clinical trials of GBM neoantigen vaccines have shown promising clinical outcomes and therefore, its rapid clinical development is warranted. Advent of newer and faster techniques such as next-generation sequencing will drive the faster clinical development of multiplex neoantigen vaccines and hence, increase in the clinical trials is expected.

KEYWORDS:

• Glioblastoma multiforme
• neoantigens
• immunotherapy
• cancer vaccines
• Rindopepimut
• precision medicine

Article Highlights

• Glioblastoma Multiforme (GBM) is type of aggressive primary brain tumor with dismal prognosis.

• Various hurdles including tumor microenvironment, pseudoprogression, immunoediting, population variability, etc. limit the successful clinical translation of many immunotherapeutics targeting GBM.

• Discovery of neoantigens and their application as personalized vaccine targets has led to a paradigm shift in cancer immunotherapy. However, it has been widely explored in ‘Hot’ tumors only.

• Results from the two phase I trials (NCT02510950, NCT02149225), assessing safety and immunogenicity of personalized neoantigen vaccines against GBM confirmed the efficacy of these vaccines against cold/low mutation burden tumors such as GBM.

• Multiple trials evaluating combinatorial approach with neoantigen vaccines against GBM have been initiated, also later phase development of these vaccines as monotherapy is expected.

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

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

Author contributions

Dr. Vaishali Londhe: Content finalizing and editing.

Ms. Varada Date: Manuscript writing and figure drawing.

Additional information

Funding

This paper was not funded.