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Adoptive T-cell therapy for malignant melanoma patients with TILs obtained by ultrasound-guided needle biopsy

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Abstract

Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) can mediate objective responses in up to 50% of malignant melanoma patients with a good performance status refractory to standard treatments. Current protocols for generation of TILs rely on open surgery for access to tumor tissue. We obtained tumor material by ultrasound-guided core needle biopsy or surgery from melanoma patients with progressive disease and were able to isolate >5 × 106 TILs from 23 of 24 patients who were subsequently treated with these cells. One-third of the individual TIL-positive cultures displayed interferon gamma activity after stimulation with relevant melanoma cell lines. When expanded TILs were used for treatment in combination with daily low dose s.c. IL-2 after prior lymphodepleting chemotherapy, we observed objective clinical responses in one patient treated with TILs obtained from surgery and 4 patients treated with TILs from core biopsies. The results of this study demonstrate for the first time the potential of core biopsies for generation of relevant numbers of TILs that can mediate objective responses in patients with metastatic malignant melanoma. Ultrasound-guided core needle biopsy is a robust, safe and inexpensive approach to obtain tumor tissue for TIL generation, and is especially valuable in instances where surgery is contraindicated.

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Abbreviations

ACT:

Adoptive cell therapy

CM:

Complete media

CT:

Computed tomography

IFN:

Interferon

HEPES:

4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid)

HLA:

Human leukocyte antigen

IL-2:

Interleukin 2

PEST:

Penicillin-streptomycin

TIL:

Tumor-Infiltrating lymphocyte

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Acknowledgments

We are grateful to all patients. The Research Foundation Stiftelsen Onkologiska Klinikens i Uppsala Forskningsfond has kindly supported this study. This study was supported by grants to Prof. T. H. Tötterman from the Swedish Cancer Society, Uppsala University and Hospital (ALF) and Lion’s Cancer Fund.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Oncology, Radiology and Radiation Science, Uppsala University, 751 85, Uppsala, Sweden

    Gustav J. Ullenhag & Gunnar Wagenius

  2. Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, 751 85, Uppsala, Sweden

    Arian M. Sadeghi, Björn Carlsson & Thomas H. Tötterman

  3. Department of Radiology and Radiation Science, Uppsala University, 751 85, Uppsala, Sweden

    Håkan Ahlström & Firas Mosavi

Authors
  1. Gustav J. Ullenhag
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  2. Arian M. Sadeghi
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  3. Björn Carlsson
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  4. Håkan Ahlström
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  5. Firas Mosavi
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  6. Gunnar Wagenius
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  7. Thomas H. Tötterman
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Corresponding author

Correspondence to Gustav J. Ullenhag.

Additional information

Gustav J. Ullenhag and Arian M. Sadeghi contributed equally to this paper.

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Ullenhag, G.J., Sadeghi, A.M., Carlsson, B. et al. Adoptive T-cell therapy for malignant melanoma patients with TILs obtained by ultrasound-guided needle biopsy. Cancer Immunol Immunother 61, 725–732 (2012). https://doi.org/10.1007/s00262-011-1182-4

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  • DOI: https://doi.org/10.1007/s00262-011-1182-4

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