title: Treatment of stage IIIB non-small-cell lung cancer with surgery followed by infusion of tumor infiltrating lymphocytes and recombinant interleukin-2: a pilot study.
abstract: Stage IIIb non-small-cell lung cancer (NSCLC) has a poor prognosis. The median survival is approximately 6 months, and only 30% of patients are alive 1 year after diagnosis. The need for effective treatment is evident. The aim of this study was to evaluate whether the infusion of tumor-infiltrating lymphocytes (TILs), isolated from resected tumor, expanded in vitro and injected together with recombinant Interleukin-2, is feasible and may at least partially modify the poor prognosis in these patients. The infusion of TILs, derived from surgically resected NSCLC and expanded in vitro, together with subcutaneous (s.c.) injections of recombinant interleukin-2 (rIL-2) was attempted in a group of 11 patients. Treated patients were infused i.v. with in vitro expanded TILs (from 4 to 70 x 10(9) cells), and rIL-2 was injected s.c. at doses varying from 61 to 378 x 10(6) IU. Toxic side effects (fever and, in some cases, hypotension) were observed and limited the dose of rIL-2 infused. Follow-up was continued for 40 months. The mean survival time was 13.8 months. Three of five TIL-treated patients with residual disease have no evident disease after 1 year, and two of them are still alive and have no evidence of disease after 40 months. This pilot study suggests that the infusion of in vitro expanded TILs, derived from surgical samples, is feasible and seems to prolong overall survival and to control the residual disease in patients with advanced NSCLC.
authors.affiliation: Servizio di Patologia Clinica, Università di Genova, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Melioli
authors.forename: G B
authors.initials: GB
authors.lastname: Ratto
authors.forename: M
authors.initials: M
authors.lastname: Ponte
authors.forename: M
authors.initials: M
authors.lastname: Guastella
authors.forename: C
authors.initials: C
authors.lastname: Semino
authors.forename: G
authors.initials: G
authors.lastname: Fantino
authors.forename: E
authors.initials: E
authors.lastname: Tassara
authors.forename: W
authors.initials: W
authors.lastname: Pasquetti
authors.forename: C
authors.initials: C
authors.lastname: Mereu
authors.forename: F
authors.initials: F
authors.lastname: Merlo
authors.forename: G
authors.initials: G
authors.lastname: Reggiardo
authors.forename: G
authors.initials: G
authors.lastname: Morasso
authors.forename: L
authors.initials: L
authors.lastname: Santi
authors.forename: L
authors.initials: L
authors.lastname: Moretta
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000601:surgery* / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007376:Interleukin-2 / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000601:surgery* / Q000628:therapy*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011994:Recombinant Proteins / Q000627:therapeutic use*
chemical_list: D007376:Interleukin-2; D011994:Recombinant Proteins