Hil2 nog mice

The design and performance of animal experiments in the current study were in accordance with EU Directive 2010/63. PDX mice (PDXv.2 model, [23 (link)]), and were established as follows: small tumor pieces were placed under the skin on the flank of 6–15-week-old NOG mice (non-obese severe combined immune-deficient interleukin-2 chain receptor γ knockout mice, Taconic, Denmark). Tumors were measured weekly with calipers, and tumor volumes were calculated as width × width × length/2. For further transplantations or treatments, tumors were extracted, and tumor suspensions were serially passaged via subcutaneous injections to NOG mice or human IL-2 transgenic NOG (hIL2-NOG) mice (Taconic). For TIL treatments, 10 × 10⁶ RepTILs were transferred intravenously to hIL-2 NOG mice with actively growing tumors, as confirmed by caliper measurements. Trametinib was mixed into the chow at 2.5 mg/kg, resulting in an approximate dose of 0.5 mg/kg mouse per day. Trametinib treatment started around 3 weeks after RepTIL transfer.

All mouse experiments were performed in accordance with EU Directive 2010/63 (Regional Animal Ethics Committee of Gothenburg #2014-36, #2016-100, and #2018-1183). Non-obese diabetic-severe combined immune-deficient interleukin-2 chain receptor γ chain knockout mice (NOG mice, Taconic, Ry, Denmark) and human IL-2 transgenic NOG (hIL2-NOG) mice (Taconic) were used for the engraftment of tumor samples. Tumor size was monitored by caliper measurements, alternatively bioluminescent signals, using the IVIS imaging system (Perkin-Elmer). When tumor growth was confirmed by two consecutive measurements, hIL2-NOG mice were treated with autologous human tumor-infiltrating lymphocytes (TILs; 20 million cells per mouse) by intravenous injection into the tail vein. NOG mice served as untreated controls.