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Enhancement of Efficacy of Wilms’ Tumor Gene WT1 Product-derived Peptide Cancer Vaccine by Co-administration with Immunopotentiating Agents: Lessons from Mouse Models

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Inflammation and Immunity in Cancer

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Abstract

To induce and activate tumor-associated antigen-specific cytotoxic T lymphocytes (CTLs) for cancer immunity, it is important not only to select potent CTL epitopes but also to combine them with appropriate immunopotentiating agents. Wilms’ tumor gene W T1 is expressed at high levels in many kinds of hematological and solid malignancies. WT1 gene products have high immunogenicity and have been reported to serve as a promising cancer antigen for tumor-specific immunotherapy. We have started WT1 peptide vaccine clinical trials since 2001, and demonstrated that WT1 peptide can induce WT1-specific immunologic responses and the associated clinical responses. To enhance the WT1 peptide vaccine’s therapeutic efficacy, we investigated various immunopotentiating agents that co-administer with WT1 peptide vaccine, using mice models for WT1 peptide cancer immunotherapy. Mycobacterium bovis bacillus Calmette-Guérin cell wall skeleton (BCG-CWS), which is well-known to activate dendritic cells (DCs), i.e., activate innate immunity, could induce and/or activate WT1-specific CTLs in combination with WT1 peptide vaccination. Interferon (IFN)-β is a type I IFN, and is known for its various anticancer properties. Co-administration of WT1 peptide and IFN-β enhanced tumor immunity mainly through the induction of WT1-specific CTLs, enhancement of natural killer (NK) activity, and promotion of major histocompatibility complex (MHC) class I expression on the tumor cells. WT1 peptide vaccination combined with BCG-CWS or IFN-β can thus be expected to enhance the clinical efficacy of WT1 immunotherapy.

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Authors and Affiliations

  1. Department of Cancer Immunology, Osaka University Graduate School of Medicine, Osaka, Japan

    Hiroko Nakajima, Yoshihiro Oka & Fumihiro Fujiki

  2. Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka, Japan

    Yoshihiro Oka

  3. Department of Immunopathology, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan

    Yoshihiro Oka

  4. Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, Osaka, Japan

    Akihiro Tsuboi

  5. Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan

    Naoya Tatsumi & Haruo Sugiyama

  6. Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, Osaka, Japan

    Naoki Hosen & Yusuke Oji

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  1. Hiroko Nakajima
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  2. Yoshihiro Oka
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  3. Akihiro Tsuboi
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  4. Fumihiro Fujiki
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  5. Naoya Tatsumi
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  7. Yusuke Oji
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  8. Haruo Sugiyama
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Correspondence to Hiroko Nakajima .

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Editors and Affiliations

  1. Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan

    Tsukasa Seya

  2. Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan

    Misako Matsumoto

  3. Kochi Medical School, Kochi University, Nankoku, Kochi, Japan

    Keiko Udaka

  4. School of Medicine, Sapporo Medical University, Sapporo, Hokkaido, Japan

    Noriyuki Sato

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Nakajima, H. et al. (2015). Enhancement of Efficacy of Wilms’ Tumor Gene WT1 Product-derived Peptide Cancer Vaccine by Co-administration with Immunopotentiating Agents: Lessons from Mouse Models. In: Seya, T., Matsumoto, M., Udaka, K., Sato, N. (eds) Inflammation and Immunity in Cancer. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55327-4_14

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