Localization of 111indium-labeled tumor infiltrating lymphocytes to tumor in patients receiving adoptive immunotherapy. Augmentation with cyclophosphamide and correlation with response

Cancer. 1994 Mar 15;73(6):1731-7. doi: 10.1002/1097-0142(19940315)73:6<1731::aid-cncr2820730630>3.0.co;2-h.


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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cell Survival
  • Child
  • Cyclophosphamide / therapeutic use*
  • Female
  • Humans
  • Immunotherapy, Adoptive*
  • Indium Radioisotopes
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / therapeutic use*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / pathology*
  • Male
  • Melanoma / diagnostic imaging
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Melanoma / secondary
  • Melanoma / therapy*
  • Middle Aged
  • Radionuclide Imaging
  • Remission Induction
  • Skin / immunology
  • Skin / pathology
  • Tumor Cells, Cultured


  • Indium Radioisotopes
  • Interleukin-2
  • Cyclophosphamide