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The liposome of trehalose dimycolate extracted from M. bovis BCG induces antitumor immunity via the activation of dendritic cells and CD8 + T cells.
- Source :
-
Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2021 Sep; Vol. 70 (9), pp. 2529-2543. Date of Electronic Publication: 2021 Feb 11. - Publication Year :
- 2021
-
Abstract
- Intravesical Bovis bacillus Calmette-Guérin (BCG) therapy is the most effective immunotherapy for bladder cancer, but it sometime causes serious side effects because of its inclusion of live bacteria. It is necessary to develop a more active but less toxic immunotherapeutic agent. Trehalose 6,6'-dimycolate (TDM), the most abundant hydrophobic glycolipid of the BCG cell wall, has been reported to show various immunostimulatory activities such as granulomagenesis and adjuvant activity. Here, we developed cationic liposomes incorporating TDM purified from Mycobacterium bovis BCG Connaught, and we investigated the antitumor effect of the cationic liposome TDM (Lip-TDM). Lip-TDM exerted an antitumor effect in bladder cancer, colon cancer, and melanoma-bearing mouse models that was comparable or even superior to that of BCG, with no body weight loss or granuloma formation. The antitumor effect of Lip-TDM disappeared in two types of mice: those with depletion of CD8 <superscript>+</superscript> T cells, and those with knockout of macrophage-inducible C-type lectin (Mincle) which recognize TDM. Lip-TDM treatment enhanced the maturation and migration of dendritic cells in the tumor microenvironment in a Mincle-dependent manner. Our results elucidate mechanisms that underlie Lip-TDM treatment and suggest that Lip-TDM has potential as a safe and effective treatment for various cancers.<br /> (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)
- Subjects :
- Adjuvants, Immunologic
Animals
Antineoplastic Agents, Immunological chemistry
Antineoplastic Agents, Immunological isolation & purification
CD8-Positive T-Lymphocytes metabolism
Chemical Fractionation
Cord Factors chemistry
Cord Factors isolation & purification
Cytokines metabolism
Dendritic Cells metabolism
Disease Models, Animal
Female
Humans
Immunologic Factors chemistry
Immunologic Factors isolation & purification
Immunophenotyping
Infusions, Parenteral
Liposomes
Lymphocyte Activation
Mice
Molecular Structure
Solvents
Treatment Outcome
Xenograft Model Antitumor Assays
Antineoplastic Agents, Immunological administration & dosage
CD8-Positive T-Lymphocytes drug effects
CD8-Positive T-Lymphocytes immunology
Cord Factors administration & dosage
Dendritic Cells drug effects
Dendritic Cells immunology
Immunologic Factors administration & dosage
Mycobacterium bovis chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1432-0851
- Volume :
- 70
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Cancer immunology, immunotherapy : CII
- Publication Type :
- Academic Journal
- Accession number :
- 33570675
- Full Text :
- https://doi.org/10.1007/s00262-021-02870-2