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K. Teramoto



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    MO18 - NSCLC - Targeted Therapies IV (ID 116)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO18.04 - MUC1-targeted dendritic cell-based vaccines in patients with standard treatments-refractory non-small-cell lung cancer (ID 3215)

      16:30 - 16:35  |  Author(s): K. Teramoto

      • Abstract
      • Presentation
      • Slides

      Background
      MUC1, a tumor antigen, has been considered to be a promising target antigen for cancer immunotherapy because it possesses a potent immunogenicity. It is processed and presented by antigen-presenting cells in a MHC-unrestricted pattern. Dendritic cell-based vaccine immunotherapy can elicit antigen-specific cytotoxic T lymphocytes in tumor-bearing hosts, and activated cytotoxic T lymphocytes are expected to attack cancer cells. In this study, we evaluated the efficacy of MUC1-targeted dendritic cell-based vaccine immunotherapy in patients with standard treatments-refractory advanced non-small-cell lung cancer (NSCLC).

      Methods
      The eligibility criteria of this immunotherapy were as follows: histologic or cytologic evidence of NSCLC that express MUC1 protein abundantly; an Eastern Cooperative Oncology Group performance status of 0-2; advanced stage of diseases refractory to any standard cancer treatments. The dendritic cells were prepared from peripheral blood mononuclear cells with cytokines interleukin-4 and granulocyte macrophage colony stimulating factor, pulsed with MUC1 peptides, and subsequently administered to patients by subcutaneous injection. The vaccinations were repeated bi-weekly, and assessable patients were received at least 6 vaccinations. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors. Adverse events were graded according to National Cancer Institute Common Toxicity Criteria.

      Results
      From June 2005 to December 2012, 36 patients were treated with dendritic cell-based vaccines, and 25 patients (69.4%) with median age of 61 years (range, 49-84 years) were assessable for tumor responses. The cohort consisted of 14 males and 11 females, and 22 patients had adenocarcinomas; 2 patients with squamous cell carcinomas and 1 patient with pleomorphic carcinoma. Among these patients, neither complete response nor partial response was obtained. Fourteen patients had progressive disease as the best response, and 10 patients had stable disease, yielding overall disease control rate of 40.0% (95%CI=20.8-59.2). Median survival time after the vaccines was 10.0 months, and 1-year survival rate was 32.3%. Adverse events related to the vaccines were less frequent. Immunological responses could be monitored in five patients, showing that MUC1-specific cytotoxic responses of effector immune cells were achieved in all of those patients, and the population of regulatory T lymphocytes in peripheral blood cells was decreased after the vaccines.

      Conclusion
      MUC1-targeted dendritic cell-based vaccine immunotherapy is feasible, and has a potential to control the diseases in patients with refractory NSCLC.

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