| First Author | Hall MS | Year | 2022 |
| Journal | Clin Cancer Res | Volume | 28 |
| Issue | 24 | Pages | 5317-5329 |
| PubMed ID | 36215121 | Mgi Jnum | J:350315 |
| Mgi Id | MGI:7662462 | Doi | 10.1158/1078-0432.CCR-22-2103 |
| Citation | Hall MS, et al. (2022) Combination Nivolumab, CD137 Agonism, and Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes for Patients with Metastatic Melanoma. Clin Cancer Res 28(24):5317-5329 |
| abstractText | PURPOSE: Metastatic melanoma is a tumor amenable to immunotherapy in part due to the presence of antigen-specific tumor-infiltrating lymphocytes (TIL). These T cells can be activated and expanded for adoptive cell transfer (ACT), which has resulted in relatively high rates of clinical responses. Similarly, immune checkpoint inhibitors, specifically programmed cell death protein 1 (PD-1) blocking antibodies, augment antitumor immunity and increase the influx of T cells into tumors. Thus, we hypothesized that addition of PD-1 inhibition may improve the outcomes for patients undergoing ACT with TILs. PATIENTS AND METHODS: Patients with stage III/IV metastatic melanoma with unresectable disease who were anti-PD-1 treatment-naive were enrolled. TILs were generated in the presence of anti-4-1BB antibody in vitro and expanded for ACT. Patients in cohort 1 received TIL infusion followed by nivolumab. Patients in cohort 2 also received nivolumab prior to surgical harvest and during TIL production. RESULTS: A total of 11 patients were enrolled, all of whom were evaluated for response, and nine completed ACT. Predominantly CD8+ TILs were successfully expanded from all ACT-treated patients and were tumor reactive in vitro. The trial met its safety endpoint, as there were no protocol-defined dose-limiting toxicity events. The objective response rate was 36%, and median progression-free survival was 5 months. Two nonresponders who developed new metastatic lesions were analyzed to determine potential mechanisms of therapeutic resistance, which included clonal divergence and intrinsic TIL dysfunction. CONCLUSIONS: Combination therapy with TILs and nivolumab was safe and feasible for patients with metastatic melanoma and provides important insights for future therapeutic developments in ACT with TILs. |
