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Necdet Ismail Hakk? Uskent



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    P1.07 - Immunology and Immunotherapy (ID 693)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Immunology and Immunotherapy
    • Presentations: 1
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      P1.07-003 - Cytolitic Tests with Hyperimmune Patient Sera Is a Good Prognostic Tool in Racotumomab Immunotherapy in Advanced Non-Small Cell Lung Cancer (ID 7428)

      09:30 - 16:00  |  Presenting Author(s): Necdet Ismail Hakk? Uskent

      • Abstract
      • Slides

      Background:
      The preferential accumulation of NeuGcGm3 in a variety of malignant tumors, compared with healthy tissues, made this molecule as an attractive target for cancer immunotherapy . 14F7 monoclonal antibody is a highly specific IgG1 against NeuGcGM3 gangliosid. The immunohistochemical detection of NeuGcGM3 allow the potential selection of patients for specific therapy with anti-idiotype racotumomab cancer vaccine. Racotumomab is an anti-idiotype vaccine, mimics this ganglioside and triggers an immune response. Antibodies reactive to NeuGcGM3 ganglioside in the vaccinated patient’s sera have cytotoxic anti-tumor properties which can be assessed in L1210 cell line, expressing this ganglioside .

      Method:
      12 patients with advanced stage NSCLC, whose tumor tissue expressed NeuGcGM3 with 14F7 monoclonal antibody included in the study. Progressing patients, unresponsive to the 1.st line platinum doublets excluded from the study. 10 Patients received racotumomab as switch maintanance following the 1st.line chemotherapy, whereas 2 patients in Stage IIIA received Racotumomab as adjuvant. Antibodies to NeuGcGM3 have been detected with ELISA test,and cytotoxic tests was performed with hyperimmune patient’s sera in the L1210 cancer cell line expressing N-Glycol GM3, at the time of initiation, and at the 3rd,6th,9th, and 12th months of vaccination. Results of cytotoxic tests as a prognostic tool and clinical outcome of the patiens were compared. The assesment of the potential predictive value of NeuGcGM3 expressions in the tumor tissue for efficacy outcomes was also investigated.

      Result:
      Out of 12 patients, 11 patient's sera showed positive cytotoxic activity over cut off value, in NueGcGM expressing L1210 cell line. Mean PFS for these patients was 13.8(8-21) months. One patient’s PFS lasted as long as 21 months whose initial stage was IIIB. In 9 patients cytototoxic activity was progressively incresed at consecutive vaccinations on the 3rd, 6th, 9th and 12th months . There was no significant difference in between IHC staining intensities with 14F monoclonal antibody in terms of cytotoxicity results.

      Conclusion:
      As a result, we can assume that cytotoxic tests may predict prognosis in the vaccinated patients.When percentage of cytotoxicity progresivelly increase in consecutive assays, we can predict a better outcome, looking to the longer PFS of these patients.In this study we could not assess the potential predictive value of NeuGcGM3 expression in the tumor tissue for efficacy outcome, since there was no significant difference in between IHC staining intensities with 14F monoclonal antibody in terms of cytotoxicity results. However, the issue of NeuGcGM3 expression in the tumor tissue as a biomarker deserve further investigation.

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