Local Immunotherapy of Oral Cancer with LAK Cells and Interleukin 2

用Ficoll-Hypaque梯度分离口腔癌患者外周血单个核细胞(PBMC)。采用逆流离心法分离外周血淋巴细胞(PBL)和单核细胞。用含5%热灭活人AB血清的RPMI1640培养液以10~6个/ml的浓度悬浮PBL，在37ﾟC条件下，用含1000U/ml重组白介素2的RPMI1640培养液体外培养4天，获得淋巴因子激活的淋巴细胞(LAK)。1.对1例上颌窦腺样囊性癌患者进行了LAK细胞和γ-IL-2联合放射治疗的过继免疫治疗。持续动脉内输注γ-IL-2(5x105单位/天)和间断给药10^7LAK细胞两次…进行了一周多的颞浅动脉插管手术。~(60)Co照射剂量为50GY。约1.5个月后发现，首次就诊时在上颌窦内观察到的肿瘤组织完全被粘液瘤间质中的板层骨取代，其内无法检测到肿瘤组织。因此，可以认为，目前接受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，另有3例患者(2例上颌窦腺样囊性癌和2例上牙槽癌)接受LAK细胞+γ-IL-2+放疗的联合治疗，全部病例均获CR。3.对4例下牙槽癌(T4N3MO)、口咽癌(T4N1MO)、上颌骨粘液表皮样癌、下颌骨髁头周围血管外皮细胞瘤等4例患者进行了伽玛IL-2局部注射治疗，均为进展期。此后，在2例(下牙槽癌和口咽癌)肿瘤病灶内注射LAK细胞和γ-IL-2后，肿瘤生长得到一过性抑制。提示伽玛IL-2+LAK细胞联合放射治疗是治疗口腔癌的有效方法。较少

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