Local Immunotherapy of Oral Cancer with LAK Cells and Interleukin 2

采用Ficoll-Hypaque梯度法从口腔癌患者静脉血中分离外周血单个核细胞（PBMC）。采用逆流离心洗脱法分离外周血淋巴细胞（PBL）和单核细胞。将PBL以10^6个细胞/ml的密度悬浮在含有5%热灭活人AB血清的RPMI 1640培养基中，在含有1000单位/ml重组白细胞介素2的RPMI 1640生长培养基中，在37‰的温度下，体外培养4天，产生淋巴因子活化淋巴细胞（LAK）。目前LAK实验中具有40-60%细胞毒活性的LAK细胞被用于本研究。1. 一例上颌窦腺样囊性癌患者接受过继免疫治疗，包括动脉注射LAK细胞和gammaIL-2联合放疗。连续动脉内输注gammaIL-2 （5 × 10^5单位/天）和10^7 LAK细胞2次/周以上注入颞浅动脉。进行了50 GY总Co照射剂量^<60>。约1.5个月后，发现第一次就诊时上颌窦内观察到的肿瘤组织已完全被黏液瘤间质内的板层骨所取代，在板层骨内已无法检出肿瘤组织。因此，可以认为目前治疗的腺样囊性癌中存在的肿瘤细胞分化为成骨细胞，这种分化现象导致了肿瘤的治愈。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）采用与上述相似的方式，接受LAK细胞+ gammaIL-2 +放疗的联合治疗，所有病例均出现CR。3. 4例下肺泡癌（T4N3MO， IV期）、口咽癌（T4N1MO， eiv期）、上颌骨粘液表皮样癌和下颌骨髁突周围血管外皮细胞瘤均局部注射gammaIL-2（10^6单位/天）治疗，所有病例均进展。随后，在2例肿瘤病灶内，除gammaIL-2外，再注射LAK细胞。（下肺泡癌和口咽癌）导致肿瘤生长的短暂抑制。这些研究结果表明，经动脉灌注gammaIL-2 + LAK细胞联合放疗是治疗口腔癌的有效方法。少

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