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Adoptive T cell therapy combined with intralesional administrations of TG1042 (adenovirus expressing interferon-γ) in metastatic melanoma patients

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Abstract

Tumor immune escape has recently been shown to be related to the development of an immune tolerance state of the microenvironment. Cytokines activating the immune system such as IFN-γ can be used to reverse the immune escape and thus to potentiate the efficacy of immunotherapy. A clinical study was conducted in 18 stage IIIc/IV melanoma patients treated with tumor-infiltrating lymphocytes (TILs) in combination with intratumoral TG1042 injection (adenovirus expressing IFN-γ). The primary objective was to investigate the safety of treatment. Secondary objectives were to study the clinical response and translational research. The treatment was well tolerated. Among the 13 patients evaluable for tumor response, 38.5 % had an overall objective response (OOR = CR + PR) and disease control rate (DCR = CR + PR + S) of 46 %. The clinical response of the 37 targeted lesions led to an OOR of 51 % and a DCR of 75 %. Translational research on predictive markers did not significantly differ between responder and non-responder patients. However, specifically regarding injected lesions, the clinical response correlated with CD3−/CD56+ NK cells which could be activated by TG1042. Further larger studies of this combined immunotherapy are needed to confirm our findings. Intralesional TG1042 combined with antigen-selected TILs should be discussed.

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Abbreviations

ACT:

Adoptive cell therapy

AJCC:

American Joint Committee of Cancer

APC:

Allophycocyanin

CR:

Complete regression

FACS:

Fluorescence-activated cell sorting

FITC:

Fluorescein isothiocyanate

H&E:

Hematoxylin and eosin

IFN-γ:

Interferon-gamma

IL:

Interleukin

MAGE:

Melanoma-associated antigen

NCI-CTC:

National Cancer Institute Common Terminology Criteria

NK:

Natural killer

NY-ESO-1:

New York esophageal squamous cell carcinoma

P:

Progression

PE:

Phycoerythrin

PR:

Partial regression

SD:

Stable disease

TIL:

Tumor-infiltrating lymphocytes

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Acknowledgments

We thank M. Yviquel, G. Hatton and J. David from the laboratory of immunodermatology and also the laboratory of immunology from Nantes Hospital for their technical support. This study was partially funded by Transgene and Nantes Hospital.

Conflict of interest

V. Bataille and J.M. Limacher are employees of Transgene SA. Other authors have no conflict of interest to disclose.

Author information

Authors and Affiliations

  1. Dermato-Oncology Department, Nantes Hospital, 1 Place Alexis Ricordeau, 44093, Nantes Cedex 1, France

    Amir Khammari, Melanie Saint-Jean, Gaelle Quereux, Anabelle Brocard, Lucie Peuvrel & Brigitte Dreno

  2. Cancer Research Center Nantes-Angers (Inserm U892, CNRS 6299), 9 Quai Moncousu, 44093, Nantes Cedex 1, France

    Amir Khammari, Jean-Michel Nguyen, Melanie Saint-Jean, Anne-Chantal Knol, Marie-Christine Pandolfino, Gaelle Quereux, Anabelle Brocard, Lucie Peuvrel & Brigitte Dreno

  3. Cell and Gene Therapy Unit (UTCG), Nantes Hospital, 1 Place Alexis Ricordeau, 44093, Nantes Cedex 1, France

    Marie-Christine Pandolfino, Soraya Saiagh & Brigitte Dreno

  4. Biostatistic Department (PIMESP), Hôpital St Jacques - CHU Nantes, 44093, Nantes, France

    Jean-Michel Nguyen

  5. Transgene SA, Boulevard Gonthier d’Andernach, CS80166, 67405, Illkirch-Graffenstaden, France

    Vincent Bataille & Jean-Marc Limacher

Authors
  1. Amir Khammari
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  2. Jean-Michel Nguyen
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  3. Melanie Saint-Jean
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  4. Anne-Chantal Knol
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  8. Lucie Peuvrel
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  9. Soraya Saiagh
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  10. Vincent Bataille
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  11. Jean-Marc Limacher
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  12. Brigitte Dreno
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Corresponding author

Correspondence to Brigitte Dreno.

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Khammari, A., Nguyen, JM., Saint-Jean, M. et al. Adoptive T cell therapy combined with intralesional administrations of TG1042 (adenovirus expressing interferon-γ) in metastatic melanoma patients. Cancer Immunol Immunother 64, 805–815 (2015). https://doi.org/10.1007/s00262-015-1691-7

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  • DOI: https://doi.org/10.1007/s00262-015-1691-7

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