# Adoptive transfer of tumor-infiltrating lymphocytes in patients with metastatic melanoma: intent-to-treat analysis and efficacy after failure to prior immunotherapies

Source: https://onco.cc/key-papers/paper-besser-til-melanoma-intent-to-treat-ccr-2013/  
OnCo record `paper-besser-til-melanoma-intent-to-treat-ccr-2013` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Sheba's decade of growing melanoma patients' own tumour-fighting cells and giving them back, reported honestly: counting everyone who enrolled, not only those who made it to treatment.

## Summary

The Ella Lemelbaum Institute at Sheba Medical Center began treating metastatic melanoma with autologous tumour-infiltrating lymphocytes in 2006, more than a decade before any regulator approved the approach. This report is the intent-to-treat analysis of the first 80 patients with stage IV disease enrolled in the programme.

Tumour-infiltrating lymphocyte cultures could be established for 72 of the 80. Fifty-seven were treated with unselected or young lymphocytes and high-dose interleukin-2 after non-myeloablative lymphodepleting conditioning. Twenty-three were withdrawn, mostly because they deteriorated clinically during the weeks the cells were being grown, which is the cost of a manufacturing step that cannot be hurried.

The overall response rate was 29 percent and median survival 9.8 months counting everyone enrolled; 40 percent and 15.2 months counting those actually treated. Five patients achieved complete and 18 partial remission. Every complete responder remained in unmaintained remission at a median follow-up of 28 months, and three-year survival among responders was 78 percent. On multivariate analysis, lactate dehydrogenase, sex, days of culture and the total number of infused CD8-positive cells independently predicted outcome. Thirty-two patients received ipilimumab before or after the cells; patients who had not responded to ipilimumab or interleukin-2 did about as well on cell therapy as those who had.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Journal: Clinical Cancer Research
- Year: 2013
- DOI: 10.1158/1078-0432.ccr-13-0380
- Authors: Besser MJ, Shapira-Frommer R, Itzhaki O, Treves AJ, Zippel DB, Levy D, Kubi A, Shoshani N, Zikich D, Ohayon Y, Ohayon D, Shalmon B, Markel G, Yerushalmi R, Apter S, Ben-Nun A, Schachter J, et al.
- Findings: Cultures established for 72 of 80 enrolled patients; 57 treated; 23 withdrawn, mainly through clinical deterioration during manufacture.; Overall response rate 29 percent and median survival 9.8 months on intent to treat; 40 percent and 15.2 months among treated patients.; Five complete and 18 partial remissions; all complete responders in unmaintained remission at a median 28 months; three-year survival among responders 78 percent.; Lactate dehydrogenase, sex, days of cells in culture and total infused CD8-positive cells were independent predictors of outcome.; Failure of prior ipilimumab or interleukin-2 did not predict failure of cell therapy.
- What it means: It showed that a single academic centre outside the United States could run tumour-infiltrating lymphocyte therapy at scale and get durable remissions, and it quantified the attrition that intent-to-treat reporting exposes and single-arm treated-patient reporting hides.
- Caveats: Single-arm, single-centre and not randomised, in an era before checkpoint inhibitors became standard first-line treatment, so the comparison group is historical.; High-dose interleukin-2 and lymphodepletion make the regimen unsuitable for frail patients, and the three-week manufacturing window excluded nearly a third of those enrolled.

## Sources

- Clin Cancer Res 2013: https://doi.org/10.1158/1078-0432.ccr-13-0380
- PubMed: https://pubmed.ncbi.nlm.nih.gov/23690483/

## Connected records

- cancers: [Melanoma](https://onco.cc/cancers/melanoma/)
- fronts: [Cell Therapy](https://onco.cc/fronts/cell-therapy/)
- technologies: [TIL therapy](https://onco.cc/technologies/til-therapy/)
- institutions: [Sheba Medical Center](https://onco.cc/institutions/sheba/)
- people: [Gal Markel](https://onco.cc/people/gal-markel/), [Jacob Schachter](https://onco.cc/people/jacob-schachter/), [Michal Besser](https://onco.cc/people/michal-besser/)
- bottlenecks: [Manufacturing cost and time for living and radioactive medicines](https://onco.cc/bottlenecks/b-manufacturing-cell-therapy/)
- journals: [Clinical Cancer Research](https://onco.cc/journals/clinical-cancer-research/)

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