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  • Long-lasting disease stabilization in the absence of toxicity in metastatic lung cancer patients vaccinated with an HLA-A2-restricted epitope derived from indoleamine 2,3 dioxygenase

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Poster Presentation
Long-lasting disease stabilization in the absence of toxicity in metastatic lung cancer patients vaccinated with an HLA-A2-restricted epitope derived from indoleamine 2,3 dioxygenase
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  1. Trine Z Iversen1,2,
  2. Lotte Engell-Noerregaard1,2,
  3. Eva Ellebaek1,2,
  4. Rikke Andersen1,2,
  5. Stine K Larsen1,
  6. Jon Bjoern1,2,
  7. Claus Zeyher3,
  8. Cécile Gouttefangeas4,
  9. Birte M Thomsen5,
  10. Bente Holm2,
  11. Per thor Straten1,
  12. Anders Mellemgaard2,
  13. Mads H Andersen1 and
  14. Inge M Svane1,2
  1. Aff1 grid.411900.d0000000406468325Center for Cancer Immune Therapy, Department of HaematologyCopenhagen University Hospital at Herlev Herlev Denmark
  2. Aff2 grid.411900.d0000000406468325Department of OncologyCopenhagen University Hospital at Herlev Herlev Denmark
  3. Aff3 grid.10392.390000000121901447Interfaculty Institute of BiochemistryUniversity of Tübingen Tübingen Germany
  4. Aff4 grid.10392.390000000121901447Interfaculty Institute of Cell Biology Department of ImmunologyUniversity of Tübingen Tübingen Germany
  5. Aff5 grid.411702.10000000093508874Department of PathologyBispebjerg Hospital Copenhagen Denmark

https://doi.org/10.1186/2051-1426-1-S1-P273

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    Meeting abstracts

    Purpose

    To investigate targeting of indoleamine 2.3 dioxygenase (IDO) enzyme using a synthetic peptide vaccine administered to patients with metastatic non small-cell lung cancer (NSCLC).

    Experimental design

    In a clinical phase I study we treated 15 HLA-A2 positive patients with stage III-IV NSCLC in disease stabilization (SD) after standard chemotherapy. Patients were treated with Imiquimod ointment and subcutaneous vaccinations (100 µg IDO5 peptide, sequence ALLEIASCL, formulated in 900 µL Montanide). Primary end point was toxicity. Clinical benefit and immunity were assessed as secondary endpoints.

    Results

    No severe toxicity was observed. One patient developed a partial response (PR) after 1 year of vaccine treatment while long-lasting disease stabilization (SD≥8.5 months) was demonstrated in another 6 patients. The median overall survival (OS) was 25.9 months. Patients demonstrated significant improved OS (P=0.03) when compared to the group of patients excluded due to HLA-A2 negativity. IDO specific CD8+ T cell immunity was demonstrated by IFN-γ Elispot and Tetramer staining. FACS analyses demonstrated a significant reduction of the Treg population (P=0.03) and a significant increase in NK cell population (P=0.05) after the 6th vaccine (2.5 months) compared to pre-treatment levels. Furthermore, expression of IDO was detected in 9/10 tumour biopsies by immunohistochemistry. HPLC analyses of Kynurenine/Tryptophan (Kyn/Trp) ratio in sera were performed. In long term analyses of two clinical responding patients the ratio of Kyn/Trp remained stable.

    Conclusion

    The vaccine was well-tolerated with no severe toxicity occurring. A median OS of 25.9 months was demonstrated and long-lasting PR+SD were seen in 47% of the patients.