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The application of exosomes as a nanoscale cancer vaccine.

Tan A, De La Peña H, Seifalian AM - Int J Nanomedicine (2010)

Bottom Line: However, they are, strictly speaking, not 'true' cancer vaccines as they are prophylactic rather than therapeutic, are only effective against the oncogenic viruses, and do not kill the actual cancer cells.On April 2010, a new prostate cancer vaccine Provenge(®) (sipuleucel-T) was approved by the US FDA, and it is the first approved therapeutic vaccine that utilizes antigen-presenting cell technology involving dendritic cells in cancer immunotherapy.Coupled with nanotechnology, engineered exosomes are emerging as new and novel avenues for cancer vaccine development.

View Article: PubMed Central - PubMed

Affiliation: Centre for Nanotechnology and Regenerative Medicine, University College London, London, UK.

ABSTRACT
Cancer is a leading cause of death globally, and it is predicted and projected to continue rising as life expectancy increases. Although patient survival rates for some forms of cancers are high due to clinical advances in treatment protocols, the search for effective cancer vaccines remains the ultimate Rosetta Stone in oncology. Cervarix(®), Gardasil(®), and hepatitis B vaccines are currently employed in preventing certain forms of viral cancers. However, they are, strictly speaking, not 'true' cancer vaccines as they are prophylactic rather than therapeutic, are only effective against the oncogenic viruses, and do not kill the actual cancer cells. On April 2010, a new prostate cancer vaccine Provenge(®) (sipuleucel-T) was approved by the US FDA, and it is the first approved therapeutic vaccine that utilizes antigen-presenting cell technology involving dendritic cells in cancer immunotherapy. Recent evidence suggests that the use of nanoscale particles like exosomes in immunotherapy could form a viable basis for the development of novel cancer vaccines, via antigen-presenting cell technology, to prime the immune system to recognize and kill cancer cells. Coupled with nanotechnology, engineered exosomes are emerging as new and novel avenues for cancer vaccine development. Here, we review the current knowledge pertaining to exosome technology in immunotherapy and also seek to address the challenges and future directions associated with it, in hopes of bringing this exciting application a step closer toward an effective clinical reality.

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Related in: MedlinePlus

Exosomes are observed on the surface of glioblastoma cells. Tumor-specific peptides or antigens from TEX can be purified and pulsed onto dendritic cells for immunotherapy. Copyright © 2008, Nature Publishing Group. Reproduced with permission from Skog J, Wurdinger T, van Rijn S, et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008;10(12):1470–1476.
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f5-ijn-5-889: Exosomes are observed on the surface of glioblastoma cells. Tumor-specific peptides or antigens from TEX can be purified and pulsed onto dendritic cells for immunotherapy. Copyright © 2008, Nature Publishing Group. Reproduced with permission from Skog J, Wurdinger T, van Rijn S, et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008;10(12):1470–1476.

Mentions: Similarly, TEX are exosomes purified from cancerous cells. TEX contains tumor antigens, and they have been shown to stimulate cells of the immune system and reduce tumor growth.36 There is also evidence pointing toward TEX as tumor and RNA transporters, which could serve as a useful biomarker and diagnostic tool (Figure 5).37 It has been shown that TEX expressing heat shock protein-70 (Hsp70) upregulates T helper cell 1 (Th1)-mediated tumor response.38 Furthermore, it has also been reported that membrane-bound Hsp70 TEX are more efficacious than cytoplasmic Hsp70 TEX.39 Evidence indicates that more potent immune responses are mounted toward vesicle-bound antigen compared to soluble antigen, and the mode of secretion can determine immunogenicity. 40 Interestingly, induction of apoptosis in cancer cells via notch signaling41 and PI3K/Akt/GSK-3β survival pathways42 is observed when TEX interacts with pancreatic cancer cells. Apart from stimulating the adaptive immune system by cross-priming cytotoxic T cells,43 it has also been demonstrated that TEX can activate the innate immune system by increasing IgG antibody response44 and NK cells.45


The application of exosomes as a nanoscale cancer vaccine.

Tan A, De La Peña H, Seifalian AM - Int J Nanomedicine (2010)

Exosomes are observed on the surface of glioblastoma cells. Tumor-specific peptides or antigens from TEX can be purified and pulsed onto dendritic cells for immunotherapy. Copyright © 2008, Nature Publishing Group. Reproduced with permission from Skog J, Wurdinger T, van Rijn S, et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008;10(12):1470–1476.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2990382&req=5

f5-ijn-5-889: Exosomes are observed on the surface of glioblastoma cells. Tumor-specific peptides or antigens from TEX can be purified and pulsed onto dendritic cells for immunotherapy. Copyright © 2008, Nature Publishing Group. Reproduced with permission from Skog J, Wurdinger T, van Rijn S, et al. Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008;10(12):1470–1476.
Mentions: Similarly, TEX are exosomes purified from cancerous cells. TEX contains tumor antigens, and they have been shown to stimulate cells of the immune system and reduce tumor growth.36 There is also evidence pointing toward TEX as tumor and RNA transporters, which could serve as a useful biomarker and diagnostic tool (Figure 5).37 It has been shown that TEX expressing heat shock protein-70 (Hsp70) upregulates T helper cell 1 (Th1)-mediated tumor response.38 Furthermore, it has also been reported that membrane-bound Hsp70 TEX are more efficacious than cytoplasmic Hsp70 TEX.39 Evidence indicates that more potent immune responses are mounted toward vesicle-bound antigen compared to soluble antigen, and the mode of secretion can determine immunogenicity. 40 Interestingly, induction of apoptosis in cancer cells via notch signaling41 and PI3K/Akt/GSK-3β survival pathways42 is observed when TEX interacts with pancreatic cancer cells. Apart from stimulating the adaptive immune system by cross-priming cytotoxic T cells,43 it has also been demonstrated that TEX can activate the innate immune system by increasing IgG antibody response44 and NK cells.45

Bottom Line: However, they are, strictly speaking, not 'true' cancer vaccines as they are prophylactic rather than therapeutic, are only effective against the oncogenic viruses, and do not kill the actual cancer cells.On April 2010, a new prostate cancer vaccine Provenge(®) (sipuleucel-T) was approved by the US FDA, and it is the first approved therapeutic vaccine that utilizes antigen-presenting cell technology involving dendritic cells in cancer immunotherapy.Coupled with nanotechnology, engineered exosomes are emerging as new and novel avenues for cancer vaccine development.

View Article: PubMed Central - PubMed

Affiliation: Centre for Nanotechnology and Regenerative Medicine, University College London, London, UK.

ABSTRACT
Cancer is a leading cause of death globally, and it is predicted and projected to continue rising as life expectancy increases. Although patient survival rates for some forms of cancers are high due to clinical advances in treatment protocols, the search for effective cancer vaccines remains the ultimate Rosetta Stone in oncology. Cervarix(®), Gardasil(®), and hepatitis B vaccines are currently employed in preventing certain forms of viral cancers. However, they are, strictly speaking, not 'true' cancer vaccines as they are prophylactic rather than therapeutic, are only effective against the oncogenic viruses, and do not kill the actual cancer cells. On April 2010, a new prostate cancer vaccine Provenge(®) (sipuleucel-T) was approved by the US FDA, and it is the first approved therapeutic vaccine that utilizes antigen-presenting cell technology involving dendritic cells in cancer immunotherapy. Recent evidence suggests that the use of nanoscale particles like exosomes in immunotherapy could form a viable basis for the development of novel cancer vaccines, via antigen-presenting cell technology, to prime the immune system to recognize and kill cancer cells. Coupled with nanotechnology, engineered exosomes are emerging as new and novel avenues for cancer vaccine development. Here, we review the current knowledge pertaining to exosome technology in immunotherapy and also seek to address the challenges and future directions associated with it, in hopes of bringing this exciting application a step closer toward an effective clinical reality.

Show MeSH
Related in: MedlinePlus