Recent progress in peptide vaccination in cancer with a focus on non-small-cell lung cancer

Abstract

Active immunotherapy aimed at the stimulation of tumor-specific T cells has established itself within the clinic as a therapeutic option to treat cancer. One strategy is the use of so-called peptides that mimic genuine T-cell epitopes as vaccines to activate tumor-specific T cells. In various clinical trials, different types of vaccines, adjuvants and other immunomodulatory compounds were evaluated in patients with different types of tumors. Here, we review the trials published in the last 3 years focusing on the T-cell response, the effect of immunomodulation and potential relationships with clinical outcomes. Furthermore, we would like to make a case for the development of peptide vaccines aiming to treat non-small-cell lung cancer, the most common cause of cancer mortality.

Keywords::

• cancer
• clinical trial
• immunotherapy
• non-small-cell lung cancer
• peptide vaccine

Financial & competing interests disclosure

This work was supported by a grant of ZonMw (nr 40-00703-98-11626) to M Talebian Yazdi. The authors are employed by the Leiden University Medical Center, which holds a patent on the use of synthetic long peptides as vaccine (US 7.202.034). SH van der Burg is named as inventor on this patent. 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.

No writing assistance was utilized in the production of this manuscript.

Key issues

• There is an increase in therapeutic peptide vaccination studies that report an association between the T-cell responses and clinical benefit. As most studies are not randomized or placebo-controlled, these correlations may reflect an overall better fitness of the patient translating in stronger immunity against vaccination, a bias that may be controlled by simultaneous measurements of the general immune status.

• Personalized multipeptide vaccines, either being overlapping peptides of tumor-associated antigens or a mix of defined epitopes based on naturally presented HLA class I- and II-restricted (mutated) peptides, hold great promise as clinical benefit is most often seen when a broad T-cell response is induced against the epitopes expressed by tumor cells.

• The future of therapeutic vaccines lies in its combined use with immunomodulators such as toll-like receptor ligands and interferons from the innate immune system, its combined use with checkpoint antibodies to alleviate the suppression of T-cell expansion and function and its combined use with chemotherapy of which many compounds do not affect the lymphocyte population but do seem to affect suppressive innate immune cells.