LOCALIZATION OF INDIUM-111-LABELED TUMOR-INFILTRATING LYMPHOCYTES TO TUMOR IN PATIENTS RECEIVING ADOPTIVE IMMUNOTHERAPY

Background. The adoptive transfer of interleukin-2 (IL-2)-cultured tum or infiltrating lymphocytes (TIL) can cause tumor regression in patien ts with metastatic melanoma. Methods. Thirty-eight patients with metas tatic melanoma receiving high dose IL-2 and TIL were studied for the a bility of autologous In-111-labeled TIL to localize to metastatic tumo r deposits by gamma camera imaging and biopsy. Single bolus cyclophosp hamide was administered 24-36 hours before TIL infusion in 27 treatmen t courses. Results. Tumor localization by In-111-labeled TIL was seen by gamma camera imaging in 26 (68.4%) treatment courses. In a univaria te analysis of factors influencing TIL traffic, cyclophosphamide admin istration was significantly associated with the ability to localize tu mor by radionuclide imaging (P2 = 0.026). Twenty-one of 26 (80.8%) tre atment courses given with cyclophosphamide demonstrated tumor localiza tion, compared with only 5 of 12 (41.7%) treatment courses without cyc lophosphamide. In addition, patients whose In-111-labeled TIL imaged t heir tumor received significantly more TIL than did those that did not (P2 = 0.0052). Biopsies revealed a greater accumulation of In-111 in cutaneous tumors than in normal skin biopsy specimens (0.0021 and 0.00 04% injectate/gram of tissue, respectively; P2 = <0.001). The median t umor-to-normal-skin ratio of simultaneous biopsies was 5.0. Finally, 1 0 of 26 (38.5%) patients who had tumor localization by scan had a clin ical response, whereas no responses were noted in 12 patients whose tu mors 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 tumor s imaged with In-111-TIL. Cyclophosphamide administration before TIL a nd IL-2 therapy and the administration of large numbers of TIL appear to improve the frequency of TIL localization to tumor.