Adoptive cell therapy with tumor-infiltrating lymphocytes supported by checkpoint inhibition across multiple solid cancer types

Anders Handrup Kverneland, Christopher Aled Chamberlain, Troels Holz Borch, Morten Nielsen, Sofie Kirial Mørk, Julie Westerlin Kjeldsen, Cathrine Lund Lorentzen, Lise Pyndt Jørgensen, Lene Buhl Riis, Christina Westmose Yde, Özcan Met, Marco Donia, Inge Marie Svane*

*Corresponding author af dette arbejde
25 Citationer (Scopus)

Abstract

Background Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) has shown remarkable results in malignant melanoma (MM), while studies on the potential in other cancer diagnoses are sparse. Further, the prospect of using checkpoint inhibitors (CPIs) to support TIL production and therapy remains to be explored. Study design TIL-based ACT with CPIs was evaluated in a clinical phase I/II trial. Ipilimumab (3 mg/kg) was administered prior to tumor resection and nivolumab (3 mg/kg, every 2 weeks ×4) in relation to TIL infusion. Preconditioning chemotherapy was given before TIL infusion and followed by low-dose (2 10e6 international units (UI) ×1 subcutaneous for 14 days) interleukin-2 stimulation. Results Twenty-five patients covering 10 different cancer diagnoses were treated with in vitro expanded TILs. Expansion of TILs was successful in 97% of recruited patients. Five patients had sizeable tumor regressions of 30%-63%, including two confirmed partial responses in patients with head-and-neck cancer and cholangiocarcinoma. Safety and feasibility were comparable to MM trials of ACT with the addition of expected CPI toxicity. In an exploratory analysis, tumor mutational burden and expression of the alpha-integrin CD103 (p=0.025) were associated with increased disease control. In vitro tumor reactivity was seen in both patients with an objective response and was associated with regressions in tumor size (p=0.028). Conclusion High success rates of TIL expansion were demonstrated across multiple solid cancers. TIL ACTs were found feasible, independent of previous therapy. Tumor regressions after ACT combined with CPIs were demonstrated in several cancer types supported by in vitro antitumor reactivity of the TILs. Trial registration numbers NCT03296137, and EudraCT No. 2017-002323-25.

OriginalsprogEngelsk
Artikelnummere003499
TidsskriftJournal for ImmunoTherapy of Cancer
Vol/bind9
Udgave nummer10
ISSN2051-1426
DOI
StatusUdgivet - 4 okt. 2021

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