Griffith K D, Read E J, Carrasquillo J A, Carter C S, Yang J C, Fisher B, Aebersold P, Packard B S, Yu M Y, Rosenberg S A
Department of Transfusion Medicine, National Cancer Institute, Bethesda, MD 20892.
J Natl Cancer Inst. 1989 Nov 15;81(22):1709-17. doi: 10.1093/jnci/81.22.1709.
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.
对接受环磷酰胺（CPM）、肿瘤浸润淋巴细胞（TIL）和白细胞介素-2（IL-2）治疗的转移性黑色素瘤患者，研究其用铟-111标记的TIL或外周血淋巴细胞（PBL）通过γ相机成像和活检在肿瘤部位定位的能力。18例患者接受了19次放射性标记TIL输注，而5例患者在TIL治疗期间接受了放射性标记的自体PBL。在接受铟-111-TIL的患者所进行的18个核扫描系列中，13个可见明显的肿瘤定位，而接受铟-111-PBL的患者，四个扫描序列中只有一个成像出肿瘤。对接受铟-111-TIL的10例患者完成了19对肿瘤和正常皮肤活检，而对接受铟-111-PBL的3例PBL患者进行了8次活检。TIL组每克肿瘤组织中定位的总注射活性平均百分比为0.0049%，PBL组为0.0010%（P2 = 0.0004）。铟-111-TIL组肿瘤与正常皮肤的平均比值是铟-111-PBL组的三倍（P2 = 0.0072）。对一名患者在CPM、TIL和IL-2的三个连续治疗疗程中进行了核扫描研究。他最初在几个部位通过铟-111-TIL显示出明显的肿瘤定位，然后在单个部位通过铟-111-PBL显示出微弱的定位，随后在重复输注铟-111-TIL时在多个部位出现阳性肿瘤成像。这些结果证实并扩展了我们最初的数据，表明经CPM预处理并随后给予IL-2的人TIL优先定位于肿瘤部位，并表明TIL的这种定位比PBL更强。
