In vivo distribution of adoptively transferred indium- 111- labeled tumor infiltrating lymphocytes and peripheral blood lymphocytes in patients with metastatic melanoma

Patients with metastatic melanoma undergoing therapy with cyclophosphamide (CPM), tumor-infiltrating lymphocytes (TIL), and interleukin-2 (IL-2) were studied for the ability of their ¹¹¹In-labeled TIL or peripheral blood lymphocytes (PBL) to localize in sites of tumor using gamma camera imaging and biopsies. Nineteen infusions of radiolabeled TIL were given to 18 patients, while five patients received radiolabeled autologous PBL during TIL therapy. Clear tumor localization was seen on 13 of 18 nuclear scan series performed on ¹¹¹In-TIL recipients, while tumor was imaged in only one of four scan sequences on patients given ¹¹¹In-PBL. Nineteen paired biopsies of tumor and normal skin were completed on 10 patients receiving ¹¹¹In-TIL, while eight biopsies were done on three PBL patients receiving ¹¹¹In-PBL. The mean percentage of total injectate activity localizing per gram of tumor tissue was 0.0049% in the TIL group and 0.0010% in the PBL group (P₂ =.0004). The mean of the tumor to normal skin ratios of the ¹¹¹In-TIL group was three times that for ¹¹¹In-PBL (P₂ =.0072). One patient was studied by nuclear scanning on three consecutive treatment courses of CPM, TIL, and IL-2. He initially demonstrated clear tumor localization by ¹¹¹In-TIL at several sites, then faint localization with ¹¹¹In-PBL at a single site, and subsequently positive tumor imaging on repeat ¹¹¹In-TIL infusion at multiple sites. These results confirm and expand our initial data demonstrating that human TIL transferred with CPM pretreatment and followed by IL-2 preferentially localize to tumor sites and indicate that this localization is greater for TIL than PBL. [J Natl Cancer Inst 81:1709-1717, 1989]