Cationized liposomal keto-mycolic acids isolated from Mycobacterium bovis bacillus Calmette-Guérin induce antitumor immunity in a syngeneic murine bladder cancer model.
Animals
BCG Vaccine
/ administration & dosage
CD4-Positive T-Lymphocytes
/ immunology
CD8-Positive T-Lymphocytes
/ immunology
Cancer Vaccines
/ administration & dosage
Cell Line, Tumor
Female
Humans
Immunotherapy
Keto Acids
/ administration & dosage
Liposomes
/ administration & dosage
Lymphocytes, Tumor-Infiltrating
/ immunology
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Nude
Molecular Structure
Mycolic Acids
/ administration & dosage
Particle Size
Urinary Bladder Neoplasms
/ drug therapy
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
27
09
2018
accepted:
30
11
2018
entrez:
5
1
2019
pubmed:
5
1
2019
medline:
1
10
2019
Statut:
epublish
Résumé
Intravesical therapy using Mycobacterium bovis bacillus Calmette-Guérin (BCG) is the most established cancer immunotherapy for bladder cancer. However, its underlying mechanisms are unknown. Mycolic acid (MA), the most abundant lipid of the BCG cell wall, is suspected to be one of the essential active components of this immunogenicity. Here, we developed cationic liposomes incorporating three subclasses (α, keto, and methoxy) of MA purified separately from BCG, using the dendron-bearing lipid D22. The cationic liposomes using D22 were efficiently taken up by the murine bladder cancer cell line MB49 in vitro, but the non-cationic liposomes were not. Lip-kMA, a cationic liposome containing keto-MA, presented strong antitumor activity in two murine syngeneic graft models using the murine bladder cancer cell lines MB49 and MBT-2 in comparison to both Lip-aMA and Lip-mMA, which contained α-MA and methoxy-MA, respectively. Interestingly, Lip-kMA(D12), which was made of D12 instead of D22, did not exhibit antitumor activity in the murine syngeneic graft model using MB49 cells, although it was successfully taken up by MB49 cells in vitro. Histologically, compared to the number of infiltrating CD4 lymphocytes, the number of CD8 lymphocytes was higher in the tumors treated with Lip-kMA. Antitumor effects of Lip-kMA were not observed in nude mice, whereas weak but significant effects were observed in beige mice with natural killer activity deficiency. Thus, a cationized liposome containing keto-MA derived from BCG induced in vivo antitumor immunity. These findings will provide new insights into lipid immunogenicity and the underlying mechanisms of BCG immunotherapy.
Identifiants
pubmed: 30608942
doi: 10.1371/journal.pone.0209196
pii: PONE-D-18-28262
pmc: PMC6319727
doi:
Substances chimiques
BCG Vaccine
0
Cancer Vaccines
0
Keto Acids
0
Liposomes
0
Mycolic Acids
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0209196Déclaration de conflit d'intérêts
Hideyasu Kiyohara is employed by Japan BCG Laboratory, Kiyose, Japan. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. There are no other competing interests to declare.
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