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Telomerase peptide vaccination: a phase I/II study in patients with non-small cell lung cancer

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Abstract

Purpose: A phase I/II study was conducted to investigate the safety, tolerability and clinical response to vaccination with a combination of telomerase peptides GV1001 (hTERT: 611–626) and HR2822 (hTERT: 540–548) in patients with non-small cell lung cancer. Experimental design: Twenty-six patients with non-small cell lung cancer received intradermal administrations of either 60 nmole (112 μg) or 300 nmole (560 μg) GV1001 in combination with 60 nM (68.4 μg) HR2822 and granulocyte macrophage-colony stimulating factor. The treatment period was 10 weeks. Booster vaccinations with 300 nM GV1001 were offered as follow-up. Monitoring of blood samples, clinical examination and radiological staging were performed regularly. Immune responses were measured as delayed-type hypersensitivity skin reaction and in vitro T cell proliferation. Bone marrow function was monitored in long time survivors. Results: The treatment was well tolerated with minor side effects. No bone marrow toxicities were observed in long time survivors with immune responses. Immune responses against GV1001 were detected in 11 of 24 evaluable patients during the primary regimen and in additional two patients following booster injections. Two patients responded to HR2822. Cloned GV1001-specific CD4+ T cells displayed a Th1 cytokine profile and recognized autologous antigen presenting cells pulsed with recombinant telomerase protein. A complete tumor response was observed in one patient who developed GV1001-specific cytotoxic T cells that could be cloned from peripheral blood. Conclusion: The results demonstrate that GV1001 and HR2822 are immunogenic and safe to use in patients with NSCLC. Induction of GV1001-specific immune responses may result in objective tumor responses. Based on these initial encouraging results, further clinical studies of GV1001 in NSCLC patients are warranted.

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Notes

  1. In the study protocol GV1001 is referred to as HR2802

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Acknowledgements

We thank Kari Lislerud for excellent technical assistance, and Mericon AS for monitoring of the study. This work has been supported by grants from The Norwegian Cancer Society (IS), the Norwegian Research Council and was supported by GemVax AS.

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Authors and Affiliations

  1. Norwegian Radium Hospital, University of Oslo, Oslo, Norway

    Paal F. Brunsvig, Steinar Aamdal, Marianne K. Gjertsen, Gunnar Kvalheim, Carrie J. Markowski-Grimsrud, Ingunn Sve, Marianne Dyrhaug, Sissel Trachsel & Gustav Gaudernack

  2. GemVax AS, Oslo, Norway

    Mona Møller & Jon A. Eriksen

  3. Gustav Gaudernack, Head of Section for Immunotherapy, Institute for Cancer Research, The Norwegian Radium Hospital, 0310, Oslo, Norway

    Gustav Gaudernack

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  1. Paal F. Brunsvig
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  2. Steinar Aamdal
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  3. Marianne K. Gjertsen
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  4. Gunnar Kvalheim
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  5. Carrie J. Markowski-Grimsrud
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  7. Marianne Dyrhaug
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  8. Sissel Trachsel
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  9. Mona Møller
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  10. Jon A. Eriksen
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  11. Gustav Gaudernack
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Corresponding author

Correspondence to Gustav Gaudernack.

Additional information

The clinical trial was supported by the Norwegian Research Council, Oslo, Norway and by GemVax AS, Oslo, Norway.

The study has been presented in part: ASCO, abstract no 666, Chicago May 2003. ASCO, abstract no 2580, Orlando May 2005.

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Brunsvig, P.F., Aamdal, S., Gjertsen, M.K. et al. Telomerase peptide vaccination: a phase I/II study in patients with non-small cell lung cancer. Cancer Immunol Immunother 55, 1553–1564 (2006). https://doi.org/10.1007/s00262-006-0145-7

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