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

Barbara A Pockaj, R. M. Sherry, J. P. Wei, J. R. Yannelli, C. S. Carter, S. F. Leitman, J. A. Carasquillo, S. M. Steinberg, S. A. Rosenberg, J. C. Yang

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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 (P = 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.

Original languageEnglish (US)
Pages (from-to)1731-1737
Number of pages7
JournalCancer
Volume73
Issue number6
StatePublished - 1994
Externally publishedYes

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Keywords

  • cyclophosphamide
  • immunotherapy
  • melanoma
  • radio imaging
  • tumor infiltrating lymphocytes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Pockaj, B. A., Sherry, R. M., Wei, J. P., Yannelli, J. R., Carter, C. S., Leitman, S. F., Carasquillo, J. A., Steinberg, S. M., Rosenberg, S. A., & Yang, J. C. (1994). Localization of 111indium-labeled tumor infiltrating lymphocytes to tumor in patients receiving adoptive immunotherapy: Augmentation with cyclophosphamide and correlation with response. Cancer, 73(6), 1731-1737.