You are here

  • Home
  • Archive
  • Volume 2, Issue Suppl 3
  • Preliminary analysis of immune responses in patients enrolled in a Phase II trial of Cyclophosphamide with Allogenic DRibble Vaccine Alone (DPV-001) or with GM-CSF or Imiquimod for adjuvant treatment of Stage IIIA or IIIB NSCLC

Article Text

Article menu

Download PDFPDF

Poster Presentation
Preliminary analysis of immune responses in patients enrolled in a Phase II trial of Cyclophosphamide with Allogenic DRibble Vaccine Alone (DPV-001) or with GM-CSF or Imiquimod for adjuvant treatment of Stage IIIA or IIIB NSCLC
  1. Traci Hilton1,
  2. Rachel Sanborn2,
  3. Brian Boulmay3,
  4. Rui Li2,
  5. Bradley Spieler3,
  6. Kyle Happel3,
  7. Christopher Paustian2,
  8. Tarsem Moudgil2,
  9. Christopher Dubay2,
  10. Brenda Fisher2,
  11. Eileen Mederos3,
  12. Augusto Ochoa3,
  13. Walter J Urba2,
  14. Hong-Ming Hu2 and
  15. Bernard Fox2
  1. Aff1 grid.438792.3UbiVac USA
  2. Aff2 grid.415337.7Robert W. Franz Cancer Research Center, Earle A. Chiles Research InstituteProvidence Cancer Center Portland OR USA
  3. Aff3 grid.279863.10000000089541233Stanley S. Scott Cancer CenterSchool of Medicine, LSUHSC New Orleans LA USA

http://dx.doi.org/10.1186/2051-1426-2-S3-P249

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Meeting abstracts

    Background

    Tumor-derived autophagosomes, DRibbles, are novel cancer vaccines that have been shown to be effective in preclinical models of established tumors. We hypothesize that DRibbles' efficacy stems from their ability to present stabilized tumor-derived short-lived proteins (SLiPs) and defective ribosomal products (DRiPs) that are normally not processed and presented by professional antigen presenting cells (APCs). These SLiPs and DRiPs represent a potential pool of tumor antigens against which the host is not tolerant. The DPV-001 vaccine packages at least 40 putative cancer antigens, including twelve antigens from the NCI's list of prioritized antigens, multiple DAMPs and agonist activity for TLR 2, 3, 4, 7 and 9 into stable double membrane microvesicles. These microvesicles have surface f-actin and spectrin that target DRibbles to CLEC9A+ APCs, the most effective APC at cross-priming immunity.

    Methods and Results

    Patients are vaccinated at 3-week intervals with a total of 7 doses. PBMCs and serum are collected at baseline and at each vaccination. Immune monitoring panels are run on peripheral whole blood to evaluate lymphocyte populations and their activation. PBMCs from the baseline visit and week 12 are treated with DRibbles (vaccine and control) to measure vaccine specific cytokine production. Patient serum from the baseline visit and week 12 is analyzed for antibody response to >9000 human proteins with ProtoArrays. We have identified multiple induced and increased antibody responses, after vaccination (n = 2 patients). UbiLT3 and UbiLT6 mutations were compared to lung adenocarcinoma (LUAD) patient mutations in the TCGA database (http://www.cbioportal.org/public-portal/data_sets.jsp) to identify mutations shared with the DPV-001 vaccine (UbiLT3 average 78.6; UbiLT6 average 73.9 shared SNPs, excluding dbSNP (common) variants). http://www.syfpeithi.de/bin/MHCServer.dll/EpitopePrediction.htm was used to find the ligation strength of reference and mutated sequences on HLA types in order to predict potential T cell epitopes.

    Conclusions

    The DPV-001 vaccine provides a source of broad-spectrum relevant antigens. Preliminary analyses of patients receiving the DPV-001 vaccine show effects on T cells and increased humoral antibody responses at 12 or 13 weeks. The DPV-001 vaccine contains mutations shared with NSCLC patients in the TCGA database, including mutations with increased immunogenicity that represent potential therapeutic targets.

    Clinical trial identifier

    NCT01909752

    Support

    R44 CA121612-02A1