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M. McAfee



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    P3.03 - Poster Session with Presenters Present (ID 473)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
    • Presentations: 1
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      P3.03-063 - Phase 1/2 Trial of WT1 TCR-Transduced Central Memory and Naïve CD8+T Cells for Patients with Mesothelioma and Non-Small Cell Lung Cancer (ID 5740)

      14:30 - 14:30  |  Author(s): M. McAfee

      • Abstract

      Background:
      The Wilms’ tumor gene (WT1) is important in cell survival and overexpressed in mesothelioma and lung cancer, providing rationale for WT1-targeted strategies.

      Methods:
      Patients with metastatic/unresectable, previously-treated mesothelioma or non-small cell lung cancer, HLA-A0201+, receive two infusions of WT1 TCR-transduced CD8+T cells at a central memory(T~CM~): naïve(T~N~) 1:1 ratio comprising each infusion. The first infusion is 1x10[9]/m[2 ]cells, to assess tolerability. The second infusion is given two weeks later at 1x10[10]/m[2], preceded by cyclophosphamide 300mg/m2/day x 2 days, and followed by interleukin-2 250,000 IU/m2 subcutaneously b.i.d x 14 days.

      Results:
      Figure 1Figure 2Six pleural mesothelioma patients have been treated to date. Four patients are evaluable; two are in progress. All patients experienced grade 1-3 cytokine release syndrome and grade 3/4 lymphopenia, which resolved. At 12 weeks, there was 1 partial response (Fig.1), 1 stable disease, and 2 with progressive disease. WT1+T cells were detectable in the peripheral blood of all 4 patients post-infusions, however only the partial responder had long-term T cell persistence to day 70 and ongoing (Fig.2). Evaluation of phenotypic/functional T cell markers and the relative persistence of T~CM ~:T~N ~subpopulations in peripheral blood is underway.





      Conclusion:
      Targeting WT1 with TCR-engineered CD8+T cells demonstrates early evidence of tolerability and anti-tumor activity in mesothelioma.