• Patients must be 18 to 75 years of age inclusive, at the time of signing the informed consent.

• Patients with pathologically confirmed previously treated refractory or recurrent stage 3-4 melanoma, which cannot be treated with curative intent with available therapies.

• Patients who have had at least 1 prior line of medical treatment (eg, checkpoint inhibitors, kinase inhibitors, IL-2). Multiple prior therapies (eg, surgery, checkpoint inhibitors, kinase inhibitors, IL-2, interferon, chemotherapy, radiation) are allowed.

• Patients must have a demonstrated WHO/ECOG performance score of 0-1 at screening.

• A tumor of \>9 mm in diameter (typically a minimum of 1 cm3 in volume), without signs of necrosis, must be available for biopsy/operation to enable growing of TILs.

• At least 1 additional tumor (\>14 mm in diameter) must be available for injections and biopsies for correlative analyses. The disease burden must be evaluable according to RECIST 1.1.

• Patients must have adequate hepatic, cardiac, and renal function as follows:

∙ Platelets ≥ 100,000/µl and \< 700,000/µl

‣ Hemoglobin ≥100 g/L

‣ AST and ALT ≤2.5×ULN

‣ GFR \>60 mL/min (CKD-EPI)

‣ Leukocytes (WBC) \>3.0G/L

‣ Absolute neutrophil count greater than 1500/mm3 without the support of filgrastim

‣ Bilirubin \<1.5×ULN

‣ Patients of 60 years or older, or have a history of ischemic heart disease, chest pain, or clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, heart block, will undergo cardiac evaluation: LVEF assessment with documented LVEF ≥ 50% by either TTE (trans thoracal echocardiography) or MUGA (multigated acquisition scan). Further cardiac evaluations in patients with cardiac risk factors (e.g. diabetes, hypertension, obesity) will be evaluated by the investigator as deemed necessary.

• Must be willing to use adequate forms of contraception from screening, during the study, and for a minimum of 90 days after the end of treatment, in accordance with the following:

∙ Woman of childbearing potential: Barrier contraceptive method (ie, condom) must be used in addition to 1 of the following methods: Intrauterine devices or hormonal contraception (oral contraceptive pills, implants, transdermal patches, vaginal rings or long-acting injections).

‣ Women not of childbearing potential: Barrier contraceptive method (ie, condom) must be used.

‣ Men: Barrier contraceptive method (ie, condom) must be used.

• Patients must be capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

⁃ Patients must be capable of understanding and complying with the parameters outlined in the protocol.

⁃ Patients must have a life expectancy longer than 3 months.

⁃ Patients must be eligible for adoptive T-cell therapy with Lymphocyte-depleting chemotherapy and TILs.