Author of

• 25943

  +

  P2.06 - Mesothelioma (Not CME Accredited Session) (ID 955)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall

  • 27034

    +

    P2.06-25 - Combined Immune Checkpoint Blockade in Malignant Pleural Mesothelioma: In Vivo Validation of in Vitro Results (ID 12075)

    16:45 - 18:00  |  Author(s): Elly Marcq
    • Abstract
    • Slides

    Background
    

    Till today, human malignant pleural mesothelioma (MPM) remains an aggressive cancer with a poor prognosis due to the limited impact on overall survival of the current treatments. Data from us and others about the presence of the immune checkpoint-related molecules PD-1, PD-L1, TIM-3 and LAG-3 in MPM lay the basis to evaluate their suitability as immunotherapeutic targets. Two clinical trials that investigated PD-1 and PD-L1 inhibition in mesothelioma (KEYNOTE-28, JAVELIN trial) have shown promising results with room for improvement. It is of great interest to investigate the effect of combined treatments and compare them to stand-alone treatment to select the best therapeutic strategy for MPM.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    Human cell lines representative for the epithelioid (NCI-H2818 and NCI-H2795) and sarcomatoid (NCI-H2731) subtypes of MPM were placed in allogeneic co-cultures with healthy donor peripheral blood mononuclear cells. The co-cultures were treated with the following immune checkpoint blocking antibodies: anti PD-1 (Nivolumab^®, BMS) or anti PD-L1 (Durvalumab^®, AstraZeneca) in combination with anti TIM-3 or anti LAG-3. Supernatant was collected and enzyme-linked immunosorbent assays and multiplex electrochemo-luminescence were used to look at the secretion of 7 cytokines, being IFNg, IL-2/5/6/10, IL-1b and TNF-a, as well as the enzyme granzyme B. Statistical analysis was done to investigate the differences between the treatment conditions.

    4c3880bb027f159e801041b1021e88e8 Result
    

    Treatment with immune checkpoint blockers as monotherapy or in combination resulted in a significant increase in the secretion of granzyme B and the cytokines IFNg, IL-2, IL-5 and IL-10. Although the increased secretion was not always statistically significant for all 3 MPM cell lines of the two subtypes, the same trends were observed among them. Interestingly, highest concentrations of granzyme B and these 4 cytokines were noticed for monotherapy treatment with anti PD-1, anti PD-L1 or either of these antibodies with anti TIM-3. In vivo investigation of PD-1 or PD-L1 blockade in combination with TIM-3 or LAG-3 blockade is currently ongoing to validate our in vitro results.

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    Our data show that treatment with anti PD-1, anti PD-L1 or their respective combination with anti TIM-3 resulted in the highest secretion of cytokines and granzyme B, suggesting that these treatments stimulate the antitumor response the most. In vivo experiments are currently ongoing for validation.

    6f8b794f3246b0c1e1780bb4d4d5dc53

    Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.