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

检查点抑制支持肿瘤浸润淋巴细胞过继细胞疗法,适用于多种实体癌类型

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作者: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

Background

Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) has shown remarkable

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.

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).

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