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Virus-like particles for vaccination against cancer.

ABSTRACT: Active immunotherapy of cancer aims to treat the disease by inducing effective cellular and humoral immune responses. Virus-like particle-based vaccines have evolved dramatically over the last few decades, greatly reducing morbidity and mortality of several infectious diseases and expectedly preventing cervical cancer caused by human papilloma virus. In contrast to these broad successes of disease prevention, therapeutic cancer vaccines remain to demonstrate clinical benefit. Yet, several preclinical and clinical trials have revealed promising results and are paving the way for medical breakthroughs. This study reviews and discusses the recent preclinical development and clinical trials in this field. This article is categorized under: Biology-Inspired Nanomaterials > Protein and Virus-Based Structures Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

SUBMITTER: Mohsen MO

PROVIDER: S-EPMC6916610 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Virus-like particles for vaccination against cancer.

Mohsen Mona O MO Speiser Daniel E DE Knuth Alexander A Bachmann Martin F MF

Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology 20190827 1

Active immunotherapy of cancer aims to treat the disease by inducing effective cellular and humoral immune responses. Virus-like particle-based vaccines have evolved dramatically over the last few decades, greatly reducing morbidity and mortality of several infectious diseases and expectedly preventing cervical cancer caused by human papilloma virus. In contrast to these broad successes of disease prevention, therapeutic cancer vaccines remain to demonstrate clinical benefit. Yet, several precli ...[more]

PMID: 31456339

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Project description:UnlabelledA vaccine capable of protecting at-risk persons against infections due to Cryptococcus neoformans and Cryptococcus gattii could reduce the substantial global burden of human cryptococcosis. Vaccine development has been hampered though, by lack of knowledge as to which antigens are immunoprotective and the need for an effective vaccine delivery system. We made alkaline extracts from mutant cryptococcal strains that lacked capsule or chitosan. The extracts were then packaged into glucan particles (GPs), which are purified Saccharomyces cerevisiae cell walls composed primarily of β-1,3-glucans. Subcutaneous vaccination with the GP-based vaccines provided significant protection against subsequent pulmonary infection with highly virulent strains of C. neoformans and C. gattii. The alkaline extract derived from the acapsular strain was analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS), and the most abundant proteins were identified. Separation of the alkaline extract by size exclusion chromatography revealed fractions that conferred protection when loaded in GP-based vaccines. Robust Th1- and Th17-biased CD4(+) T cell recall responses were observed in the lungs of vaccinated and infected mice. Thus, our preclinical studies have indicated promising cryptococcal vaccine candidates in alkaline extracts delivered in GPs. Ongoing studies are directed at identifying the individual components of the extracts that confer protection and thus would be promising candidates for a human vaccine.ImportanceThe encapsulated yeast Cryptococcus neoformans and its closely related sister species, Cryptococcus gattii, are major causes of morbidity and mortality, particularly in immunocompromised persons. This study reports on the preclinical development of vaccines to protect at-risk populations from cryptococcosis. Antigens were extracted from Cryptococcus by treatment with an alkaline solution. The extracted antigens were then packaged into glucan particles, which are hollow yeast cell walls composed mainly of β-glucans. The glucan particle-based vaccines elicited robust T cell immune responses and protected mice from otherwise-lethal challenge with virulent strains of C. neoformans and C. gattii. The technology used for antigen extraction and subsequent loading into the glucan particle delivery system is relatively simple and can be applied to vaccine development against other pathogens.

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Virus-like particles for vaccination against cancer.

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Virus-like particles for vaccination against cancer.

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