進行性腎癌に対するLAK(Lymphokine-Activated Killer)療法 : 動注療法の臨床成績とLAK細胞活性に関する基礎的検討

Abstract

転移性腎腺癌に対して, 全身性および局所動注によるLAK治療を行った。動注による短時間であるが, 転移巣へLAK細胞を施行させることが可能であった。低濃度のγIL-2(106U/day, 2X)併用化のLAK動注療法では骨や軟部組織を中心とした9例, 16転移巣を治療しCR, PR, MRを含めて8転移巣に有効であった。全身性LAK療法は肺転移巣に効果がなかった。抗癌剤およびIFNはともにLAK療法を規定する因子となる。LAK細胞はin vivoで腫瘍細胞と一定時間培養することによりIFN-γやTNF-αを産生する。手術不能な肺転移巣にIFNや全身性LAK療法が適応となるが, カテーテル留置可能の栄養動脈を確保できれば, LAKの動注が, 出来ないときにIFNが適応となる。TNF-αの産出で脳転移巣の出現に注意する必要がある

Experimental and clinical studies were conducted on lymphokine-activated killer (LAK) cell therapy for advanced renal cell carcinoma (RCC). The traffic assay using radiolabeled LAK cells indicated short-term but appreciable accumulation of LAK cells in the tumor site when trans-arterially infused. By contrast, systemically infused LAK cells were localized not to the tumor tissue but to the lung. Therefore, we began treatment of the patients with extrapulmonary metastases by means of regional arterial administration of LAK cells and those who had pulmonary metastases by a systemic LAK therapy. Regimen of Interleukin-2 (IL-2) administration was bolus infusion of 5 x 10 U IL-2 twice daily. Frequency of LAK cell administration varied from one to three times a week depending upon the patient's condition. Eight out of 16 metastases, such as bone, muscle, and lymph node metastases, in 9 patients treated by arterial LAK therapy showed regression. Side effects during LAK therapy were not serious. Past history of having chemotherapy was an unfavorable factor that could reduce the sensitivity to LAK therapy. Our laboratory study showed the production of Interferon (IFN)-gamma and Tumor Necrosis Factor (TNF)-alpha by LAK cells when preincubated with RCC cells, which may indicate the mechanism of LAK cell-mediated antitumor activity in vivo. The study also showed that LAK cells as well as monocytes preincubated with the supernatant of LAK cells damaged normal endothelial cells in vitro, which suggested the possibility that LAK therapy risks increasing the frequency of brain metastasis by damaging the blood-brain barrier.(ABSTRACT TRUNCATED AT 250 WORDS)