Modification of lymphokine-activated killer cell accumulation into tumor sites by chemotherapy, local irradiation, or splenectomy.

Molecular biotherapy Pub Date : 1990-12-01
A Kawata, M Hosokawa, Y Sawamura, K Ito, Y Une, T Shibata, J Uchino, H Kobayashi
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Abstract

The effects of chemotherapy or local irradiation on lymphokine-activated killer (LAK) cell accumulation into tumor sites were investigated. Lymphokine-activated killer cells labeled with 111In-oxine were injected into the caudal vein of C57BL/6 mice that had been previously transplanted with 3LL cancer. An adoptive transfer of LAK cells was carried out 4 days after treatments. Twenty-four hours after the transfer, tumor tissues were excised, and the accumulation of labeled LAK cells in the tumor was measured. In two different experiments, LAK cell accumulation in tumor in the nontreated group was 2.15% and 1.58% of the administered dose per gram of tissue. The accumulation in the groups of mice treated with cyclophosphamide, nimustine hydrochloride, or Adriamycin increased fourfold (7.38% dose/g, 6.61% dose/g), threefold (6.47% dose/g) and twofold (4.46% dose/g), respectively, as compared with the nontreated group. These agents induced significant tumor regression. In the group treated with bleomycin, which showed no significant effect on tumor growth, LAK cell accumulation in tumor remained unaltered (1.57% dose/g). However, the group treated with local irradiation, which induced significant tumor reduction, showed no increase in LAK cell accumulation into tumors. These results suggest that some antitumor drugs enhance LAK cell accumulation into tumor sites and that this increase is due to tumor modification by antitumor drugs.

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化疗、局部照射或脾切除术对淋巴因子激活的杀伤细胞在肿瘤部位积聚的影响。
研究了化疗或局部照射对淋巴因子激活杀伤细胞(LAK)在肿瘤部位积聚的影响。将111In-oxine标记的淋巴因子激活的杀伤细胞注射到先前移植了3LL癌的C57BL/6小鼠的尾静脉中。处理4天后进行LAK细胞过继转移。转移24小时后,切除肿瘤组织,测量标记LAK细胞在肿瘤中的积累情况。在两个不同的实验中,未治疗组肿瘤中的LAK细胞积累量分别为每克组织给药剂量的2.15%和1.58%。环磷酰胺组、盐酸尼莫司汀组、阿霉素组小鼠累积量分别比未给药组增加4倍(7.38%剂量/g、6.61%剂量/g)、3倍(6.47%剂量/g)和2倍(4.46%剂量/g)。这些药物诱导了显著的肿瘤消退。博来霉素组对肿瘤生长无明显影响,肿瘤内LAK细胞蓄积量保持不变(1.57%剂量/g)。然而,局部照射组,诱导肿瘤显著缩小,LAK细胞在肿瘤中的积累没有增加。这些结果表明,一些抗肿瘤药物增加LAK细胞在肿瘤部位的积累,这种增加是由于抗肿瘤药物对肿瘤的修饰。
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