Abstracts of the 28th Annual Scientific Meeting of the Society for Immunotherapy of Cancer (SITC)
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Genetically engineered lymphocytes in metastatic melanoma: TIL 1383I TCR transduced T-cells are detectable after infusion
Journal for ImmunoTherapy of Cancer volume 1, Article number: P31 (2013)
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.
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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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Regan, C., Nishimura, M., Clark, A.L. et al. Genetically engineered lymphocytes in metastatic melanoma: TIL 1383I TCR transduced T-cells are detectable after infusion. j. immunotherapy cancer 1, P31 (2013). https://doi.org/10.1186/2051-1426-1-S1-P31
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Keywords
- Melanoma
- Metastatic Melanoma
- Melanoma Patient
- Fludarabine
- Human Albumin
