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Establishment of adoptive cell therapy with tumor infiltrating lymphocytes for non-small cell lung cancer patients

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Abstract

Adoptive cell therapy (ACT) of tumor infiltration lymphocytes (TIL) yields promising clinical results in metastatic melanoma patients, who failed standard treatments. Due to the fact that metastatic lung cancer has proven to be susceptible to immunotherapy and possesses a high mutation burden, which makes it responsive to T cell attack, we explored the feasibility of TIL ACT in non-small cell lung cancer (NSCLC) patients. Multiple TIL cultures were isolated from tumor specimens of five NSCLC patients undergoing thoracic surgery. We were able to successfully establish TIL cultures by various methods from all patients within an average of 14 days. Fifteen lung TIL cultures were further expanded to treatment levels under good manufacturing practice conditions and functionally and phenotypically characterized. Lung TIL expanded equally well as 103 melanoma TIL obtained from melanoma patients previously treated at our center, and had a similar phenotype regarding PD1, CD28, and 4-1BB expressions, but contained a higher percent of CD4 T cells. Lung carcinoma cell lines were established from three patients of which two possessed TIL cultures with specific in vitro anti-tumor reactivity. Here, we report the successful pre-clinical production of TIL for immunotherapy in the lung cancer setting, which may provide a new treatment modality for patients with metastatic NSCLC. The initiation of a clinical trial is planned for the near future.

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Abbreviations

ACT:

Adoptive cell therapy

CM:

Complete medium

REP:

Rapid expansion procedure

TIL:

Tumor infiltrating lymphocytes

TRC:

Tissue remnant culture

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Funding

The authors would like to thank Haya and Nehemia Lemelbaum for their generous support.

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Authors and Affiliations

  1. Department of Thoracic Surgery, Sheba Medical Center, 52621, Ramat Gan, Israel

    Ronny Ben-Avi & Alon Ben-Nun

  2. Ella Lemelbaum Institute for Immuno-Oncology, Sheba Medical Center, 52621, Ramat Gan, Israel

    Ronit Farhi, Marina Gorodner, Eyal Greenberg, Gal Markel, Jacob Schachter, Orit Itzhaki & Michal J. Besser

  3. Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Gal Markel & Michal J. Besser

Authors
  1. Ronny Ben-Avi
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  2. Ronit Farhi
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  3. Alon Ben-Nun
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  4. Marina Gorodner
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  5. Eyal Greenberg
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  6. Gal Markel
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  7. Jacob Schachter
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  8. Orit Itzhaki
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  9. Michal J. Besser
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Contributions

RB-A, OI, and MJB designed the study. RB-A, OI, RF, AB-N, MG, and EG acquired the data. RB-A, OI, RF, GM, JS, and MJB analyzed and interpreted the data. All the authors revised the work, approved the final version, and agreed to be accountable of the work.

Corresponding authors

Correspondence to Orit Itzhaki or Michal J. Besser.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The protocol was approved by the IRB Committee of the Sheba Medical Center, Israel. Approval number: SMC-0921-13.

Informed consent

Patients signed an informed consent under the approved protocol SMC-0921-13.

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Ben-Avi, R., Farhi, R., Ben-Nun, A. et al. Establishment of adoptive cell therapy with tumor infiltrating lymphocytes for non-small cell lung cancer patients. Cancer Immunol Immunother 67, 1221–1230 (2018). https://doi.org/10.1007/s00262-018-2174-4

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  • DOI: https://doi.org/10.1007/s00262-018-2174-4

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