CAF05: cationic liposomes that incorporate synthetic cord factor and poly(I:C) induce CTL immunity and reduce tumor burden in mice

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• 作者：Jon Hansen (1) joa@ssi.dk
  Thomas Lindenstr?m (1)
  Julie Lindberg-Levin (1)
  Claus Aagaard (1)
  Peter Andersen (1)
  Else Marie Agger (1)
• 关键词：Adjuvant – CTL – Vaccine – Mouse tumor – CAF01 – CAF05
• 刊名：Cancer Immunology, Immunotherapy
• 出版年：2012
• 出版时间：June 2012
• 年：2012
• 卷：61
• 期：6
• 页码：893-903
• 全文大小：633.6 KB
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• 作者单位：1. Infectious Disease Immunology, Statens Serum Institut, Building 81/306, 2300 Copenhagen S, Denmark
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Cancer Research
  Immunology
  Oncology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0851

文摘

Considerable effort has been put into targeting tumors through therapeutic vaccination using dendritic cell-, DNA-, protein-, or peptide-based vaccines. Purified peptides and proteins are generally not immunogenic and need to be administered with an adjuvant that will trigger an appropriate immune response. Safe adjuvants that favor induction of tumor reactive CD8+ T cells with the capacity to directly kill tumor cells are therefore a high priority. We have previously reported on the effect and mechanism of a cationic adjuvant formulation, CAF01, which incorporates synthetic mycobacterial cord factor and primes protective Th1, Th17, and antibody responses in animal models of bacterial, viral, and parasitic infections. The CAF01 adjuvant is currently in clinical trial. Using CAF01 as a backbone, we recently demonstrated that incorporating the TLR3 ligand polyinosinic/polycytidylic acid [poly(I:C)] primes CD8+ T cells specific to the SIINFEKL epitope of the model antigen ovalbumin. In the present study, we demonstrate that CAF01/poly(I:C), termed cationic adjuvant formulation 05 or CAF05, can induce CD8+ T cells that efficiently lyse target cells and significantly reduce tumor growth in two different mouse tumor models: lung B16-OVA melanoma expressing ovalbumin and the self-antigen TRP2, and subcutaneous TC-1 tumors expressing the human papillomavirus-16 protein E7.