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Junping Jing



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    P2.04 - Immuno-oncology (ID 167)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.04-91 - Target Antigen Levels in NSCLC Define a Clinically Relevant Activation Threshold for NY-ESO-1<sup>c259</sup> TCR T-Cell Therapy (Now Available) (ID 2259)

      10:15 - 18:15  |  Author(s): Junping Jing

      • Abstract
      • Slides

      Background

      Chimeric antigen receptor (CAR) and T cell receptor (TCR) T cell therapies are innovative ‘living drugs’ with the potential for transformational benefit to patients. T cell therapies, have so far, shown impressive efficacy in haematological malignancies. However, treatment of solid tumours remains challenging. Unlike CARs, that recognize cell surface proteins, TCRs recognize intracellular targets presented in the context of human leukocyte antigen (HLA). NY-ESO-1 and LAGE-1a are tumour-associated intracellular antigens that generate a shared SLLMWITQC peptide bound to HLA-A*02 and expressed on multiple malignancies, including non-small cell lung cancer (NSCLC).

      Our TCR T cell product (GSK3377794) consists of autologous, lentivirally (LV) transduced T cells engineered to express an affinity enhanced NY-ESO-1c259 TCR recognizing the SLLMWITQC/HLA-A*02 peptide. Cell therapy trials with NY-ESO-1c259 TCR T cells have shown the highest objective responses to date to solid cancer in patients with synovial sarcoma, metastatic melanoma and multiple myeloma. Recently a partial response in a patient with advanced lung adenocarcinoma was reported with a another TCR-engineered T cell product targeting NY-ESO-1.

      The aims of our study were (1) to systematically assess the prevalence of target antigen expression for NY-ESO-1 and LAGE-1a in NSCLC (2) to determine the product-specific threshold of target antigen expression in NSCLC required to induce a specific T cell response, and (3) to explore means to selectively modulate NY-ESO-1/LAGE-1a expression in lung cancer with the aim of increasing patient benefit from TCR T cell treatment.

      Method

      We established and characterized a NSCLC tumour biobank consisting of: primary patient tumour tissues, patient derived xenograft (PDX) samples and tumour cell lines. Expression of HLA-A*02 was confirmed by flow cytometry and levels of NY-ESO-1/LAGE-1a were measured via RT-qPCR. GSK3377794 response against these samples was determined by IFN-γ secretion and correlated with NY-ESO-1/LAGE-1a expression levels.

      Result

      Expression of NY-ESO-1 and LAGE-1a antigen varied across the NSCLC tumour biobank samples. GSK3377794 activation correlated with NY-ESO-1/LAGE-1a expression levels in NSCLC. The functional readouts identify a product-specific antigen expression threshold for GSK3377794 in NSCLC, which could translate to a potential patient population that may benefit from GSK3377794 treatment. Our experiments further indicate that it is possible to increase NY-ESO-1/LAGE-1a expression in NSCLC cells by use of epigenetic modifiers enhancing specific targeting by GSK3377794.

      Conclusion

      To date this is the most comprehensive and systematic analysis that correlates target antigen expression in NSCLC with functional responses of GSK3377794 using a set of clinically relevant sample specimens.

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