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Poster Presentation
Genetically engineered lymphocytes in metastatic melanoma: TIL 1383I TCR transduced T-cells are detectable after infusion
  1. Courtney Regan1,
  2. Michael Nishimura1,
  3. Ann Lau Clark1,
  4. Kelly Moxley1,
  5. Gina Scurti1,
  6. Vladimir Slepushkin2,
  7. Andre Roy2,
  8. Kathy Schonely2,
  9. Boro Dropulic2 and
  10. Joseph Clark1
  1. Aff1 grid.411451.40000000122150876Cardinal Bernadin Cancer CenterLoyola University Medical Center Maywood IL USA
  2. Aff2 grid.420872.bLentigen Corporation Gaithersburg MD USA

http://dx.doi.org/10.1186/2051-1426-1-S1-P31

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    Meeting abstracts

    Background

    Previous studies in adoptive T-cell transfer have suggested that persistence of the transduced T-cells is central to making this therapy a viable option. Understanding the behavior of tumor-reactive T-cells in cancer patients and measuring persistence are two objectives in a phase I clinical trial using TCR TIL 1383I transduced T cells in stage IV melanoma patients.

    Methods

    Peripheral blood mononuclear cells (PBMCs) were isolated from a melanoma patient, activated with anti-hCD3 with rhIL2 and rhIL15, transduced with lentivirus encoding the TIL 1383I TCR, and expanded to treatment numbers. 2 x 108 transduced cells were suspended in 5% human albumin and infused over 30 minutes. The infusion was preceded by lymphodepletion with fludarabine and cyclophosphomide and followed with low dose IL-2 for one week. A modified CD34 cassette in the vector enabled monitoring of the transduced T cells in the patient’s PBMC post-infusion. PBMC were collected from patient on days 1, 3, 5, 7, 14, 25, and 35. The presence of transduced T cells at each timepoint was measured by staining with anti-CD34 mAb and analyzed using a BD LSRFortessa flow cytometer.

    Results

    Transduced T cells were detected in the patient’s blood at day 25 post infusion. 1.45% of the patients T cells were TIL 1383I TCR transduced T-cells. We estimate that at least 10% of the infused TIL 1383I TCR transduced T cells were present after 4 weeks.

    Conclusion

    Previous studies with TIL suggest better T-cell engraftment, persistence, and therapeutic efficacy with homeostatic proliferation after lymphodepletion. Out results confirm that the infused TIL 1383I TCR transduced T-cells could be detected 4 weeks after infusion. Localization of genetically engineered T-cells and ensuring their activation and function is of value in anti-tumor T-cell therapy.