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R. Maekawa



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    P3.04 - Poster Session 3 - Tumor Immunology (ID 155)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P3.04-001 - Combined adjuvant chemoimmunotherapy with CBDCA+GEM and autologous tumor lysate-transduced dendritic cell vaccinations in patients with operable NSCLC (ID 92)

      09:30 - 09:30  |  Author(s): R. Maekawa

      • Abstract

      Background
      Surgical adjuvant chemotherapy with platinum doublet is effective but not enough to suppress recurrence of NSCLC. We have applied combination chemoimmunotherapy with CBDCA+GEM and autologous tumor lysate transduced dendritic cell vaccination in patients with operable NSCLC in order to clarify that such a treatment can induce tumor specific immune response.

      Methods
      Eight patients with NSCLC whose pathological stages ranging from IB~IV were included in this study. The main purpose of the study is to obtain the principle of concept in which such vaccination can induce cellular immune response against autologous tumor cells detected by ELISPOT assay and establishment of CTL clones to recognize the tumor cell. Autologous tumor lysate was prepared from the surgical specimen aseptically by 5 times of freeze-thaw and sonication . DC cells were prepared from peripheral blood mononuclear cells obtained by apheresis, and in vitro culture with IL-4 and GM-CSF. Matured DC was induced by culture with TNF-α. Autologous tumor lysate-transduced DC was prepared by electroporation using MaxCyte cell loading system(MaxCyte[R]). More than 7x10[6] of the DC were injected intradermally at groin biweekly at 1, 3, 5, 7, 9 and 11week. Combination chemotherapy with CBDCA+GEM was administered at 0, 2, 4, 6, 8 and 10 week.

      Results
      Delayed type hypersensitivity skin reaction to the DC was observed in 5 of 8 patients after completion of the vaccination(6 times). ELISPOT assay revealed specific IFN-γ production in response to autologous tumor lysate-transduced DC following completion of the vaccination in 3 of the 5 patients. In one patient among them, CTL clones could be induced successfully in vitro, and identification of the Ag recognized by the CTL is now underway. No serious adverse effect was observed. Six patients have recurrent disease at 6, 6, 8, 10, 12 and 18months after operation. One patient(N0.6) died of the disease at 13 months after the operation due to systemic metastasis. However, the other patients are alive with(5 patients) or without(2 patients) evidence of the recurrent disease(ranging from 10~22 months as of February, 2013). Figure 1

      Conclusion
      The autologous tumor lysate-transduced DC vaccination is effective to induce tumor specific cellular immune response in some of such patients. Establishment of CTL clones recognizable autologous tumor cells can lead to identification of specific Ag coding genes which can be used as immunological targets.