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Genetically engineered lymphocytes in metastatic melanoma: TIL 1383I TCR transduced T-cells are detectable after infusion

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Journal for ImmunoTherapy of Cancer20131(Suppl 1):P31

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

Published: 7 November 2013

Keywords

  • Melanoma
  • Metastatic Melanoma
  • Melanoma Patient
  • Fludarabine
  • Human Albumin

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.

Authors’ Affiliations

(1)
Cardinal Bernadin Cancer Center, Loyola University Medical Center, Maywood, USA
(2)
Lentigen Corporation, Gaithersburg, USA

Copyright

© Regan et al; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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