Author of

• 12648

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  P3.11 - Poster Session 3 - NSCLC Novel Therapies (ID 211)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

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    P3.11-032 - A pilot single institution study of autologous tumor autophagosome (DRibble) vaccination with docetaxel in patients (pts) with stage IV non-small cell lung cancer (NSCLC) (ID 2486)

    09:30 - 09:30  |  Author(s): B. Fisher
    • Abstract

    Background
    DRibbles are tumor-derived autophagosomes containing short-lived proteins (SLiPs) and defective ribosomal products (DRiPs). Vaccination with DRibbles produces tumor regression and provides cross-protection against syngeneic MCA sarcomas in preclinical models. Docetaxel can expose hidden tumor antigens and induces relative lymphopenia, potentially enhancing specific immune response. Sargramostim (GM-CSF) augments priming of tumor-specific T cells when administered at the site of DRibble vaccine in mice. This pilot study of autologous NSCLC DRibble vaccination with GM-CSF and docetaxel enrolled patients with advanced incurable NSCLC with malignant pleural effusion.

    Methods
    Pts had NSCLC with malignant pleural effusion, ECOG PS ≤ 2, and up to 2 prior chemotherapy regimens. Prior cancer-related vaccine therapy, active autoimmune disease, HIV, viral hepatitis, or chronic steroid use were not permitted. Pts with rapid clinical deterioration after enrollment were not eligible for vaccination. After informed consent, cells from malignant pleural fluid were cultured with bortezomib to block degradation of SLiPs and DRiPs and ammonium chloride to prevent lysosomal degradation of the autophagosome. DRibble vaccines were irradiated and passed sterility and endotoxin release criteria. Pts received docetaxel 75 mg/m[2] IV on day 1 and 29 for antitumor effect and to unmask tumor antigens and produce relative lymphopenia. Vaccination was scheduled for days 14, 43, 57, 71 and 85. GM-CSF (50 ug/d) was given via mini pump for 6d after each vaccination with immune monitoring pretreatment and at each vaccination.

    Results
    Six pts (3M, 3F, average age 65) with PS 1 and adenocarcinoma were enrolled. All received d1 docetaxel. Two did not receive further therapy due to clinical decline. Four pts were vaccinated (2-4 vaccines). One of 4 pts exhibited autologous tumor-specific immune response (IFN-γ, TNF-α, IL-5, IL-10) and 3 of 4 pts generated B cell responses (>5 fold specific antibody), with 1 patient not evaluable (Table 1). Figure 1

    Conclusion
    DRibble vaccine given with GM-CSF and chemotherapy is feasible. Small patient numbers preclude further conclusions. In order to translate this strategy to a larger number of pts in a more feasible population, we have developed an allogeneic DRibble vaccine from two NSCLC cell lines expressing at least 9 NCI-prioritized cancer antigens and including agonists for TLR 2, 3, 4, 7 & 9, HSPs and a dendritic cell-targeting molecule. A phase II trial of adjuvant DRibble vaccine alone or combined with GM-CSF or imiquimod is open in patients with definitively treated stage IIIA/B NSCLC. Support R21 CA123864-02 (WJU), R444 CA121612-01 (SA/TH) and Kuni Foundation (WJU).