Microsphere priming facilitates induction of potent therapeutic T‐cell immune responses against autochthonous liver cancers. Issue 4 (16th January 2014)

• Record Type: Journal Article
• Authors: Brinkhoff, Benjamin; Ostroumov, Dmitrij; Heemcke, Jessica; Woller, Norman; Gürlevik, Engin; Manns, Michael P.; Longerich, Thomas; Zender, Lars; Harty, John T.; Kubicka, Stefan; Kühnel, Florian; Wirth, Thomas C.
• Is Part Of: European journal of immunology. Volume 44:Issue 4(2014:Apr.)
• Page Start: 1213
• Page End: 1224
• Publication Date: 2014-01-16
• Subjects: Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201343794
• Languages: English
• ISSNs: 0014-2980

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 <italic>Listeria monocytogenes</italic> 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/<italic>Listeria</italic> 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/<italic>Listeria</italic> vaccination resulted in eradication of liver tumors, long‐term survival of animals and establishment of stable cancer‐specific memory CD8<sup>+</sup> T‐cell populations. Therefore, combined PLGA/<italic>Listeria</italic> 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.</p> </abstract>