Tumour-derived exosomes as antigen delivery carriers in dendritic cell-based immunotherapy for malignant mesothelioma

Our plain-English summary of Tumour-derived exosomes as antigen delivery carriers in dendritic cell-based immunotherapy for malignant mesothelioma, by N.M. Mahaweni, M.E. Kaijen-Lambers, J. Dekkers, et al (Journal of Extracellular Vesicles, 2013).

The study

• Authors: N.M. Mahaweni, M.E. Kaijen-Lambers, J. Dekkers, J.G. Aerts, J.P. Hegmans
• Journal: Journal of Extracellular Vesicles
• Published: 2013;2
• Cited by: 102 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: In 2001, it was postulated that tumour-derived exosomes could be a potent source of tumour-associated antigens (TAA). Since then, much knowledge is gained on their role in tumorigenesis but only very recently tumour-derived exosomes were used in dendritic cell (DC)-based immunotherapy. For this, DCs were cultured ex-vivo and loaded with exosomes derived from immunogenic tumours such as melanoma or glioma and re-administrated to induce anti-tumour responses in primary and metastatic tumour mouse models. In contrast, malignant mesothelioma (MM) is a non-immunogenic tumour and because only a few mesothelioma-specific TAA are known to date, we investigated whether mesothelioma-derived exosomes could be used as antigen source in DC-based immunotherapy.

Methods: Mouse MM AB1 cells were used to generate tumour lysate and tumour-derived exosomes. Tumour lysate was generated by 5 cycles of freeze-thawing followed by sonication of AB1 cells. Tumour exosomes were collected from the AB1 cell culture supernatant and followed a stepwise ultracentrifugation. Protein quantification and electron microscopy were performed to determine the protein amount and to characterise their morphology. To test whether MM derived exosomes are immunogenic and able to stimulate an anti-tumoral response, BALB/c mice were injected with a lethal dose of AB1 tumour cells at day 0, followed by intraperitoneal injection of a single dose of DCs loaded with tumour exosomes, DCs loaded with tumour lysate, or phosphate buffered saline (PBS), at day 7.

Results: Mice which received tumour exosome-loaded DC immunotherapy had an increased median and overall survival compared to mice which received tumour lysate-loaded DC or PBS.

Conclusion: In this study, we showed that DC immunotherapy loaded with tumour exosomes derived from non-immunogenic tumours improved survival of tumour bearing mice.

In plain English

This short communication described an experiment in mice. The researchers used AB1, a mouse mesothelioma cell line derived from mice that developed mesothelioma after exposure to asbestos fibres. From it they made tumour exosomes (tiny particles released by cancer cells) and tumour lysate (broken-up cancer cells), which were loaded onto dendritic cells, a type of immune cell. Eighteen female BALB/c mice received a lethal dose of AB1 tumour cells. Seven days later, 6 got exosome-loaded dendritic cells, 6 got lysate-loaded dendritic cells and 6 got a salt solution (PBS) as a control. All control mice died within 15 days. At day 52, 16.7% of the lysate group and 33.3% of the exosome group were alive. Median survival was 13 days (control), 18.5 days (lysate) and 29.5 (exosome). The overall survival comparison was not statistically significant (p-value 0.0992), while a test for trend was reported as significant. Surviving exosome-treated mice still developed tumours. The authors concluded that exosomes improved the efficacy of this dendritic cell immunotherapy. They noted that no group received unloaded dendritic cells.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment (short communication) testing dendritic cell immunotherapy in a mouse mesothelioma model
• Who was studied: 18 female BALB/c mice, 6 per group, housed at the animal care facility of the Erasmus MC, Rotterdam, The Netherlands. They were injected with AB1 mouse mesothelioma cells.
• Exposure: No asbestos exposure was studied in this experiment. The AB1 tumour cells came from BALB/c mice that developed mesothelioma after exposure to asbestos fibres; the fibre type is not named. The treatment studied was a single injection at day 7 of dendritic cells loaded with tumour exosomes, dendritic cells loaded with tumour lysate, or PBS as control.
• Main results:
  • All mice in the PBS control group died within 15 days after tumour injection.
  • 16.7% of mice in the tumour lysate-loaded dendritic cell group and 33.3% of mice in the tumour exosome-loaded dendritic cell group survived until the end of the experiment (52 days).
  • Median survival was 13 days in the PBS group and 18.5 days in the tumour lysate-loaded dendritic cell group.
  • Median survival in the exosome-loaded dendritic cell group was 29.5 (no unit printed).
  • The log-rank (Mantel-Cox) comparison of survival across groups was not statistically significant (p-value 0.0992).
  • A log-rank test for trend was reported as significant (p 0.00342; the comparison symbol is missing from the text).
  • The surviving mice treated with exosome-loaded dendritic cells did develop tumours.
  • Tumours from the dendritic cell vaccine-treated group showed abundant infiltration by CD4 T cells, CD8 T cells and dendritic cells. This was not seen in tumours from the control group.
  • The tumour exosomes used contained less protein (6.78, units printed as mg) than the equivalent amount of tumour lysate (15.67).
• The authors' conclusion: The authors concluded that, although mesothelioma-derived exosomes contained less protein than tumour lysate, loading them onto dendritic cells improved the efficacy of dendritic cell immunotherapy in the mice.
• Limitations the authors state:
  • The experiment did not include a group of mice given unloaded dendritic cells, so it could not show that the effect depended on the exosomes.
  • The authors stated that further studies are needed to define the composition of these exosomes.

Topics

Medical terms in this study, explained in our Lexicon: Immunotherapy, Mesothelioma, Carcinogenesis, Overall Survival.

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