Phase I pilot study of Wilms tumor gene 1 peptide‐pulsed dendritic cell vaccination combined with gemcitabine in pancreatic cancer

<jats:p>This study aimed to evaluate the feasibility of and immune response to Wilms tumor gene 1 (<jats:italic><jats:styled-content style="fixed-case">WT</jats:styled-content>1</jats:italic>) peptide‐pulsed dendritic cell vaccination combined with gemcitabine (<jats:styled-content style="fixed-case">DCGEM</jats:styled-content>) as a first‐line therapy among patients with advanced pancreatic cancer. Ten <jats:styled-content style="fixed-case">HLA</jats:styled-content>‐A*2402 patients were treated with <jats:styled-content style="fixed-case">WT</jats:styled-content>1 peptide‐pulsed <jats:styled-content style="fixed-case">DC</jats:styled-content> vaccination (1 × 10<jats:sup>7</jats:sup> cells) on days 8 and 22 and gemcitabine (1000 mg/m<jats:sup>2</jats:sup>) on days 1, 8 and 15. Induction of a <jats:styled-content style="fixed-case">WT</jats:styled-content>1‐specific immune response was evaluated using the delayed‐type hypersensitivity (<jats:styled-content style="fixed-case">DTH</jats:styled-content>) skin test, interferon‐γ enzyme‐linked immunospot and <jats:styled-content style="fixed-case">HLA</jats:styled-content> tetramer assays, along with assays for various immunological factors. <jats:styled-content style="fixed-case">DCGEM</jats:styled-content> was well‐tolerated, and the relative dose intensity of gemcitabine was 87%. Disease control associated with a low neutrophil/lymphocyte ratio was observed in all three patients with <jats:styled-content style="fixed-case">DTH</jats:styled-content> positivity; it was also correlated with a low percentage of granulocytic myeloid derived suppressor cells in the pretreatment peripheral blood (<jats:italic>P</jats:italic> = 0.017). Patients with liver metastases and high levels of inflammatory markers such as C‐reactive protein and interleukin‐8 (<jats:styled-content style="fixed-case">IL</jats:styled-content>‐8) showed poor survival even though a <jats:styled-content style="fixed-case">WT</jats:styled-content>1‐specific immune response was induced in them. <jats:styled-content style="fixed-case">WT</jats:styled-content>1 peptide‐pulsed <jats:styled-content style="fixed-case">DCGEM</jats:styled-content> is feasible and effective for inducing anti‐tumor T‐cell responses. Our results support future investigations for pancreatic cancer patients with non‐liver metastases and favorable immunological conditions. This trial was registered with the University hospital Medical Information Network (UMIN) Clinical Trials Registry (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="http://www.umin.ac.jp/ctr/">http://www.umin.ac.jp/ctr/</jats:ext-link> number: UMIN‐000004855).</jats:p>