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Cara Kenney



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    P3.04 - Immunooncology (Not CME Accredited Session) (ID 970)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.04-27 - An Allogeneic Tumor Cell Lysate Vaccine Induces Immune Responses to Lung Cancer Associated Antigens: Preliminary Results of a Phase II Study (ID 14030)

      12:00 - 13:30  |  Author(s): Cara Kenney

      • Abstract
      • Slides

      Background

      Whereas lung cancers often express cancer-germline (CG) protein as well as onco-fetal carbohydrate antigens, immune responses to these antigens are limited in lung cancer patients. This trial was performed to examine if a tumor cell lysate vaccine could induce broad immunity to CG and oncofetal antigens, and to ascertain if metronomic cyclophosphamide and celecoxib (cy/cel) enhances vaccine-induced immune responses.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Freeze-thaw lysates were prepared from H1299 lung cancer cells exhibiting high level CG and oncofetal antigen expression. 11 patients with primary thoracic malignancies (6 NSCLC, 2 SCLC, 2 esophageal cancer, 1 thymoma; median age = 61 y) and 10 patients with extrathoracic neoplasms metastatic to the chest (8 sarcoma, 1 melanoma, 1 RCC; median age = 36 y) rendered NED by conventional therapy were randomized to receive lysate (10 mg protein/vaccine) with Iscomatrix™ adjuvant via deep intradermal injection q month x 6 with or without daily oral metronomic cy/cel. The primary endpoint was serologic response to a panel of purified CG as well as carbohydrate antigens assessed in a blinded manner by ELISA or glycan array techniques, respectively, 1 month after the 6th vaccination. Immune subsets were assessed in peripheral blood (p-values uncorrected for multiple comparisons). Standard of care imaging studies were obtained at baseline and 1 month after the 3rd and 6th vaccinations unless otherwise clinically indicated.

      4c3880bb027f159e801041b1021e88e8 Result

      All patients exhibited local inflammatory responses and flu-like symptoms lasting 72-96 hours following vaccinations. There were no dose limiting treatment related toxicities. 14 patients (67%) completed all six vaccinations; 7 patients were removed from study early due to disease recurrence. 8 of 14 patients (4: vaccine alone and 4: vaccine and cy/cel; 57%) exhibited serologic responses to NY-ESO-1. One patient developed antibodies to GAGE7; several patients exhibited reactivity to XAGE and MAGE-C2. Additional serologic responses were observed against Muc1, Muc1Tn, and LSTc. Vaccine therapy decreased percent Tregs (p=0.067), PD-1 expression on Tregs (p=0.023), PD-L1 expression on CD14+ monocytes (p=0.0089), PD-L1 expression on classical monocytes (p=0.0159), and PD-L1 expression on intermediate monocytes (p= 0.0031). Cy/cel did not increase immune responses or enhance vaccine-induced alterations in peripheral immune subsets.

      8eea62084ca7e541d918e823422bd82e Conclusion

      : H1299 lysate vaccines with Iscomatrix™ induce immune responses to CG and oncofetal antigens commonly expressed in lung cancers, and modulate peripheral immune subsets in a manner that may enhance antitumor immunity. These findings support further evaluation of the vaccine in combination with epigenetic agents and immune checkpoint inhibitors for lung cancer therapy.

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