title: Treatment with tumour infiltrating lymphocytes and interleukin-2 in patients with metastatic melanoma: a pilot study.
abstract: Tumour infiltrating lymphocytes (TIL) were isolated and expanded from biopsy samples of 4 patients with metastatic melanoma. The patients were treated with autologous expanded TIL and continuous or bolus infusion of Interleukin 2 (IL-2) at a dose of 18 x 10(6) International Units/m2/day for 5 days starting 36-48 hours after administration of cyclophosphamide at a dose of 1 g/m2. The number of TIL infused ranged from 10(10) to 5.56 x 10(10) cells. Two patients had stable disease (SD) lasting for 2 1/2 and 4 months respectively and they died 24 and 13 months after therapy. One patient died during therapy due to a pseudomonas septicaemia and another patient developed progressive disease (PD). He died 3 months after the start of therapy. The side effects were substantial but most of them were reversible upon cessation of the treatment. The majority of the expanded TIL of all patients were of the CD8+ phenotype. Cutaneous metastases from two patients, removed after treatment with IL-2 and TIL, showed moderate lymphocytic infiltration also mainly of CD8+ T cells. The treatment with IL-2 and TIL is feasible, but further investigations should continue in an attempt to improve the efficacy of the therapy, to reduce toxicity and to diminish the costs and labour of the culture methods.
authors.affiliation: Department of Medical Oncology, Free University Hospital Amsterdam, The Netherlands.
authors.forename: J W
authors.initials: JW
authors.lastname: Baars
authors.forename: J C
authors.initials: JC
authors.lastname: Fonk
authors.forename: R J
authors.initials: RJ
authors.lastname: Scheper
authors.forename: B M
authors.initials: BM
authors.lastname: von Blomberg-van der Flier
authors.forename: H
authors.initials: H
authors.lastname: Bril
authors.forename: P
authors.initials: P
authors.lastname: von Valk
authors.forename: H M
authors.initials: HM
authors.lastname: Pinedo
authors.forename: J
authors.initials: J
authors.lastname: Wagstaff
mesh_terms: D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D016246:Lymphocytes, Tumor-Infiltrating / Q000166:cytology / Q000276:immunology*; D008297:Male; D008545:Melanoma / Q000473:pathology / Q000556:secondary* / Q000628:therapy*; D010865:Pilot Projects
chemical_list: D007376:Interleukin-2; D003520:Cyclophosphamide