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Local Immunotherapy of Oral Cancer with LAK Cells and Interleukin 2

LAK 细胞和白细胞介素 2 治疗口腔癌的局部免疫疗法

基本信息

批准号：
63870080
负责人：
SATO Mitsunobu
金额：
$ 6.14万
依托单位：
The University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1989
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-63870080/
关键词：
Oral cancer LAK cells Interleukin 2 Local immunotherapy Subsets of peripheral blood lymphocytes Radiotherapy インターロイキン2

项目摘要

Peripheral blood mononuclear cells (PBMC) were separated on a Ficoll-Hypaque gradient from venous blood of oral cancer patients. In addition, PBMC were separated into peripheral blood lymphocytes (PBL) and monocytes by counterflow centrifugal elutriation. PBL were suspended at a density of 10^6 cells/ml in RPMI 1640 medium containing 5% heat-inactivated human AB serum and were activated to generate lymphokine-activated lymphocytes (LAK) by in vitro incubation for 4 days in the RPMI 1640 growth medium containing 1000 units/ml of recombinant interleukin 2 at 37ﾟC. The LAK cells having 40-60% of cytotoxic activity in the current LAK assay was used for the current study. 1. A patient with an adenoid cystic carcinoma of the maxillary sinus was treated by adoptive immunotherapy involving intraarterial injection of LAK cells and gammaIL-2 in combination with radiotherapy. Continuous intraarterial infusion of gammaIL-2 (5x10^5 units/day) and intermittent administration of 10^7 LAK cells twice … More a week into the superficial temporal artery were performed. A toral ^<60>Co irradiation dose of 50 GY was carried out. After about 1.5 months, it was found that the tumor tissue observed in the maxillary sinus on the first visit was completely replaced by lamellar bone in the myxomatous stroma, within which the tumor tissue could not be detected. Thus, it can be considered that the tumor cells present in the adenoid cystic carcinoma submitted to the current therapy differentiated into bone-forming cells and this differentiation phenomenon led to the cure of the tumor. 2. In addition to the above case, other three cases (two carcinomas of the upper alveolus and gingiva and an adenoid cystic carcinoma of the maxillary sinus) were submitted to the combination therapy being composed of LAK cells plus gammaIL-2 plus radiotherapy in a similar fashion as described above, resulting in CR in all cases. 3. Four cases including a carcinoma of the lower alveolus (T4N3MO; stage IV), an oropharyngeal carcinoma (T4N1MO; stageIV), a mucoepidermoid carcinoma of the maxilla and a hemangiopericytoma arising around the condyle head of mandible were treated with local injection of gammaIL-2 (10^6 units/day) into the tumor, resulting in progressive disease in all cases. Thereafter, injection of LAK cells in addition to gammaIL-2 into the tumor lesion of 2 cases.(carrinoma of the lower alveolus and oropharyngeal carcinoma) resulted in a transient inhibition of the tumor growth. These findings indicate that contihubus intraarterial infusion of gammaIL-2 plus LAK cells in combination with radiotherapy is effective as therapy of oral cancer. Less

在Ficoll-Hypaque梯度上从口腔癌患者的静脉血中分离外周血单个核细胞（PBMC）。此外，通过逆流离心淘洗将PBMC分离成外周血淋巴细胞（PBL）和单核细胞。将PBL以10^6个细胞/ml的密度悬浮于含有5%热灭活人AB血清的RPMI 1640培养基中，并通过在37 ℃下在含有1000单位/ml重组白细胞介素2的RPMI 1640生长培养基中体外孵育4天来激活以产生淋巴因子激活的淋巴细胞（LAK）。在当前LAK测定中具有40-60%细胞毒活性的LAK细胞用于当前研究。1.采用过继免疫疗法治疗上颌窦腺样囊性癌患者，包括动脉内注射LAK细胞和γ IL-2联合放疗。连续动脉内输注γ IL-2（5 × 10^5单位/天）和间断给予10^7 LAK细胞两次 ...更多信息颞浅动脉内植入。Co <60>γ射线辐照剂量为50戈伊。约1.5个月后，发现第一次就诊时在上颌窦中观察到的肿瘤组织完全被粘液瘤基质中的板层骨所取代，其中无法检测到肿瘤组织。因此，可以认为，接受当前治疗的腺样囊性癌中存在的肿瘤细胞分化成骨形成细胞，并且这种分化现象导致肿瘤的治愈。2.除上述病例外，其他3例（2例上牙槽和牙龈癌和1例上颌窦腺样囊性癌）接受由LAK细胞+ γ IL-2+放疗组成的联合治疗，所有病例均获得CR。3. 4例包括下牙槽癌（T4 N3 MO; IV期）、口咽癌（T4 N1 MO; IV期）、上颌骨粘液表皮样癌和下颌骨髁状突头周围发生的血管外皮细胞瘤，均采用局部注射γ IL-2（10^6单位/天）治疗，所有病例均出现疾病进展。2例瘤灶内注射LAK细胞和γ IL-2。（下肺泡癌和口咽癌）导致肿瘤生长的短暂抑制。提示γ-IL-2联合LAK细胞动脉灌注联合放疗治疗口腔癌是有效的。少