Volume 2 Supplement 3
Adoptive cell therapy with tumor infiltrating lymphocytes and intermediate dose IL-2 for metastatic melanoma
© Andersen et al.; licensee BioMed Central Ltd. 2014
Published: 6 November 2014
Adoptive cell therapy (ACT) with tumor infiltrating lymphocytes (TILs) achieved impressive clinical results in several single institution Phase I/II clinical trials performed outside of Europe, and holds the promise to enter the mainstream of standard melanoma care in the near future. However, although transient, the toxicities associated with high-dose interleukin-2 (IL-2) classically administered together with TILs are severe and recent results have questioned its use. To further scrutinize IL-2 dosing, we have carried out a Phase II trial using TILs after classical lymphodepletion but followed by an attenuated regimen of IL-2.
Materials and methods
A total of 25 patients with progressive metastatic melanoma, PS ≤1, age <70 and at least one resectable metastasis was included in this Phase II study (NCT00937625). TIL infusion was preceded by standard lymphodepleting chemotherapy but followed by an intravenous intermediate dose IL-2 decrescendo regimen.
The trial is fully recruited. Data indicate that the lower dose of IL-2 considerably decreased the toxicity of the treatment, and imaging evaluations of the first 22 patients evaluated showed two complete responses (29+, 16+ months) and seven partial responses (28+, 12, 20+, 12 and 11+, 8, 6+ months) with most responses still ongoing. Clinical responses were associated with high numbers of tumor reactive T cells infused. Importantly, in most responding patients we observed induction and durable persistence of anti-melanoma T cell responses in the peripheral blood. Updated results will be presented at the 2014 SITC conference.
As the first European institution we show that TIL-based ACT is reliable, logistically feasible to administer and clinically effective in metastatic melanoma. Importantly, a high response rate including long-lasting complete responses can be induced after treatment with TILs followed by an attenuated regimen of IL-2, which considerably reduced the occurrence of severe side effects. Effective TIL treatment is associated with induction and long-term persistence in the blood of T cells producing in vitro anticancer responses.
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/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.