Journal article
Microsphere priming facilitates induction of potent therapeutic T‐cell immune responses against autochthonous liver cancers
European journal of immunology, Vol.44(4), pp.1213-1224
04/2014
DOI: 10.1002/eji.201343794
PMID: 24338782
Abstract
Immunotherapy of solid tumors is often hampered by the low frequency of tumor‐specific T cells elicited by current vaccination strategies. Here, we describe a prime‐boost vaccination protocol based on the administration of antigen conjugated to poly‐lactic‐co‐glycolic acid (PLGA) microspheres followed by booster vaccination with Listeria monocytogenes vectors, which rapidly generates potent immune responses within two weeks. Compared with conventional vaccination with antigen‐pulsed dendritic cells, the use of PLGA microspheres resulted in immune responses of significantly higher magnitude, which could be further enhanced via coinjection of TLR 3 agonists. In an immunocompetent model of subcutaneous hepatocellular carcinoma, PLGA/Listeria vaccination resulted in complete remission of established tumors and prolonged survival. To further test the efficacy of the novel vaccination for the treatment of solid tumors, we developed an orthotopic liver cancer model based on the injection of transposon‐flanked plasmids expressing oncogenes and model antigens. In this transgenic mouse model of liver cancer, PLGA/Listeria vaccination resulted in eradication of liver tumors, long‐term survival of animals and establishment of stable cancer‐specific memory CD8+ T‐cell populations. Therefore, combined PLGA/Listeria vaccination holds promise as a novel immunotherapeutic option for the treatment of solid cancers and as a means to boost the therapeutic efficacy of established cancer vaccines.
Details
- Title: Subtitle
- Microsphere priming facilitates induction of potent therapeutic T‐cell immune responses against autochthonous liver cancers
- Creators
- Benjamin Brinkhoff - Medical School HannoverDmitrij Ostroumov - Medical School HannoverJessica Heemcke - Medical School HannoverNorman Woller - Medical School HannoverEngin Gürlevik - Medical School HannoverMichael P Manns - Medical School HannoverThomas Longerich - University Hospital HeidelbergLars Zender - University Hospital TübingenJohn T Harty - University of IowaStefan Kubicka - Kreiskliniken ReutlingenFlorian Kühnel - Medical School HannoverThomas C Wirth - Medical School Hannover
- Resource Type
- Journal article
- Publication Details
- European journal of immunology, Vol.44(4), pp.1213-1224
- DOI
- 10.1002/eji.201343794
- PMID
- 24338782
- ISSN
- 0014-2980
- eISSN
- 1521-4141
- Number of pages
- 12
- Grant note
- SANDER foundation SFB Transregio
- Language
- English
- Date published
- 04/2014
- Academic Unit
- Pathology
- Record Identifier
- 9984047779302771
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