title: Localization of 111indium-labeled tumor infiltrating lymphocytes to tumor in patients receiving adoptive immunotherapy. Augmentation with cyclophosphamide and correlation with response.
abstract: BACKGROUND
  The adoptive transfer of interleukin-2 (IL-2)-cultured tumor infiltrating lymphocytes (TIL) can cause tumor regression in patients with metastatic melanoma.
  
  
  METHODS
  Thirty-eight patients with metastatic melanoma receiving high dose IL-2 and TIL were studied for the ability of autologous 111In-labeled TIL to localize to metastatic tumor deposits by gamma camera imaging and biopsy. Single bolus cyclophosphamide was administered 24-36 hours before TIL infusion in 27 treatment courses.
  
  
  RESULTS
  Tumor localization by 111In-labeled TIL was seen by gamma camera imaging in 26 (68.4%) treatment courses. In a univariate analysis of factors influencing TIL traffic, cyclophosphamide administration was significantly associated with the ability to localize tumor by radionuclide imaging (P2 = 0.026). Twenty-one of 26 (80.8%) treatment courses given with cyclophosphamide demonstrated tumor localization, compared with only 5 of 12 (41.7%) treatment courses without cyclophosphamide. In addition, patients whose 111In-labeled TIL imaged their tumor received significantly more TIL than did those that did not (P2 = 0.0052). Biopsies revealed a greater accumulation of 111In in cutaneous tumors than in normal skin biopsy specimens (0.0021 and 0.0004% injectate/gram of tissue, respectively; P2 = < 0.001). The median tumor-to-normal-skin ratio of simultaneous biopsies was 5.0. Finally, 10 of 26 (38.5%) patients who had tumor localization by scan had a clinical response, whereas no responses were noted in 12 patients whose tumors were not imaged (P2 = 0.022). CONCLUSIONS. Localization in tumor may be important in the mechanism of TIL antitumor activity because no clinical responses were seen in patients who did not have their tumors imaged with 111In-TIL. Cyclophosphamide administration before TIL and IL-2 therapy and the administration of large numbers of TIL appear to improve the frequency of TIL localization to tumor.
authors.affiliation: University Hospitals of Cleveland, Department of Surgery, Ohio.
authors.forename: B A
authors.initials: BA
authors.lastname: Pockaj
authors.forename: R M
authors.initials: RM
authors.lastname: Sherry
authors.forename: J P
authors.initials: JP
authors.lastname: Wei
authors.forename: J R
authors.initials: JR
authors.lastname: Yannelli
authors.forename: C S
authors.initials: CS
authors.lastname: Carter
authors.forename: S F
authors.initials: SF
authors.lastname: Leitman
authors.forename: J A
authors.initials: JA
authors.lastname: Carasquillo
authors.forename: S M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: S A
authors.initials: SA
authors.lastname: Rosenberg
authors.forename: J C
authors.initials: JC
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002470:Cell Survival; D002648:Child; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D007205:Indium Radioisotopes; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology*; D008297:Male; D008545:Melanoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D008875:Middle Aged; D011877:Radionuclide Imaging; D012074:Remission Induction; D012867:Skin / Q000276:immunology / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D007205:Indium Radioisotopes; D007376:Interleukin-2; D003520:Cyclophosphamide