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Updated: Oct 18, 2025
Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells
Published on: March 7, 2025
Adoptive cell therapy with tumor-infiltrating lymphocytes supported by checkpoint inhibition across multiple solid
Anders Handrup Kverneland1,2, Christopher Aled Chamberlain2, Troels Holz Borch1,2
1Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark.
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.
Insights
Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) shows promise beyond melanoma. Combining TILs with checkpoint inhibitors (CPIs) demonstrated feasibility and efficacy in various solid tumors, including head-and-neck cancer.
Area of Science:
- Immunotherapy
- Oncology
- Cellular Therapy
Background:
- Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) is effective for malignant melanoma.
- Limited research exists on TIL-based ACT for other cancers.
- The role of checkpoint inhibitors (CPIs) in supporting TIL therapy is underexplored.
Purpose of the Study:
- To evaluate the safety and efficacy of TIL-based ACT combined with CPIs in patients with various solid tumors.
- To assess the feasibility of TIL expansion and treatment across different cancer types.
- To explore potential biomarkers associated with treatment response.
Main Methods:
- A clinical phase I/II trial involving 25 patients with 10 different cancer diagnoses.
- Administration of ipilimumab and nivolumab (CPIs) prior to tumor resection and TIL infusion.
- Preconditioning chemotherapy, in vitro expanded TIL infusion, and low-dose interleukin-2 stimulation.
Main Results:
- Successful TIL expansion in 97% of patients across multiple solid cancers.
- Tumor regressions (30%-63%) observed in five patients, including partial responses in head-and-neck cancer and cholangiocarcinoma.
- Exploratory analysis linked tumor mutational burden and CD103 expression to disease control, and in vitro tumor reactivity to tumor size reduction.
Conclusions:
- TIL expansion is highly successful across diverse solid tumors.
- TIL-based ACT combined with CPIs is feasible and shows efficacy in multiple cancer types.
- In vitro TIL reactivity correlates with clinical response, suggesting its potential as a predictive biomarker.
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