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
University Hospitals of Cleveland, Department of Surgery, Ohio.
Cancer. 1994 Mar 15;73(6):1731-7. doi: 10.1002/1097-0142(19940315)73:6<1731::aid-cncr2820730630>3.0.co;2-h.
The adoptive transfer of interleukin-2 (IL-2)-cultured tumor infiltrating lymphocytes (TIL) can cause tumor regression in patients with metastatic melanoma.
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.
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.
白细胞介素-2（IL-2）培养的肿瘤浸润淋巴细胞（TIL）的过继性转移可使转移性黑色素瘤患者的肿瘤消退。
对38例接受高剂量IL-2和TIL治疗的转移性黑色素瘤患者进行研究，通过γ相机成像和活检来观察自体111铟标记的TIL定位于转移性肿瘤灶的能力。在27个治疗疗程中，于TIL输注前24 - 36小时给予单次大剂量环磷酰胺。
γ相机成像显示，26个（68.4%）治疗疗程中可见111铟标记的TIL在肿瘤部位定位。在影响TIL归巢的因素单变量分析中，给予环磷酰胺与通过放射性核素成像使肿瘤定位的能力显著相关（P2 = 0.026）。给予环磷酰胺的26个治疗疗程中有21个（80.8%）显示肿瘤定位，而未给予环磷酰胺的12个治疗疗程中仅有5个（41.7%）显示肿瘤定位。此外，111铟标记的TIL在肿瘤部位成像的患者比未成像的患者接受的TIL显著更多（P2 = 0.0052）。活检显示，皮肤肿瘤中111铟的蓄积量高于正常皮肤活检标本（分别为0.0021%和0.0004%注射量/克组织；P2 = < 0.001）。同时活检的肿瘤与正常皮肤的中位比值为5.0。最后，通过扫描显示肿瘤定位的26例患者中有10例（38.5%）出现临床反应，而肿瘤未成像的12例患者未观察到反应（P2 = 0.022）。结论。肿瘤部位的定位在TIL抗肿瘤活性机制中可能很重要，因为未用111铟-TIL使肿瘤成像的患者未出现临床反应。在TIL和IL-2治疗前给予环磷酰胺以及给予大量TIL似乎可提高TIL在肿瘤部位定位的频率。
