The effect of adoptive cell therapy (ACT) with tumor infiltrating lymphocytes (TILs) has repeatedly been demonstrated in malignant melanoma and recent studies have indicated a potential in other selected cancer diagnoses. In a clinical trial (NCT03296137) we have tested the potential of TIL-based ACT across cancer types.
Twenty-five patients with 12 different cancer diagnoses were treated with ex vivo expanded TILs at Herlev University Hospital between 2017 and 2019. The ACT was preceded by a single dose of ipilimumab before tumor removal and combined with 4 doses of nivolumab before and after cell infusion. Patients were hospitalized for conditioning chemotherapy before T cell infusion followed by 14 days of low-dose interleukin-2 (IL-2).
Four patients (16%) - 2 with head-and-neck cancer, 1 cholangiocarcinoma and 1 sarcoma – obtained a partial response to therapy, 17 patients stabile disease and 4 progressive disease. Median progression-free survival was 88 days. Overall, the therapy regimen was tolerated and safe in all patients with expected side effects comparable to malignant melanoma ACT TIL trials but with the addition of immune related adverse events from the checkpoint inhibitors. The ex vivo expansion of TILs was successful in 30/31 recruited patients across cancer types with a median expansion time of 24 days. In-depth immune phenotyping of the TILs both in the tumor and after ex vivo expansion along with ex vivo anti-tumor reactivity will be presented.
Our data show that TIL-based ACT in combination with checkpoint inhibitors is safe and feasible. We show that clinical responses can be obtained in previously unreported cancer types and confirm that TIL-therapy has a potential in non-melanoma patients.
Danish Cancer Society, Knæk Cancer.
All authors have declared no conflicts of interest.