Cheever M A, Greenberg P D, Fefer A
J Immunol. 1980 May;124(5):2137-42.
In previous studies mice bearing an established transplanted syngeneic leukemia were cured by the adoptive transfer of immune lymphoid cells inoculated as an adjunct to chemotherapy, whereas nonimmune cells had no effect. By employing a smaller initial tumor inoculum to enhance the sensitivity of the chemoimmunotherapy model, the current study demonstrated that cells from normal nonimmune donors can also eradicate tumor. Thus, adult BALB/c mice given a lethal dose (1 x 10(4)) of LSTRA on day 0 were treated on day 5 with cyclophosphamide (CY) alone or CY plus nonimmune cells. Untreated mice all died by day 10. Cy alone prolonged median survival time (MST) to day 20, but all mice died. Treatment with CY plus 1 x 10(7) nonimmune cells prolonged the MST to day 26 and cured 16 of 48 mice. The effector cells, present in the spleens of normal and nude mice, were nonadherent lymphocytes resistant to anti Thy + C. These results are consistent with this effector cell in adoptive chemoimmunotherapy being an NK cell. However, they are distinct from classical NK cells since they are not directly cytotoxic in vitro in a short term CRA and do not neutralize tumor in vivo in a Winn assay.
在先前的研究中,已建立移植性同基因白血病的小鼠通过接受作为化疗辅助手段接种的免疫淋巴细胞的过继转移而被治愈,而非免疫细胞则无此效果。通过采用较小的初始肿瘤接种量以提高化学免疫疗法模型的敏感性,当前研究表明来自正常非免疫供体的细胞也能够根除肿瘤。因此,于第0天给予致死剂量(1×10⁴)LSTRA的成年BALB/c小鼠在第5天接受单独环磷酰胺(CY)或CY加非免疫细胞的治疗。未治疗的小鼠在第10天全部死亡。单独使用CY可将中位生存时间(MST)延长至第20天,但所有小鼠最终均死亡。用CY加1×10⁷非免疫细胞进行治疗可将MST延长至第26天,并使48只小鼠中的16只被治愈。存在于正常小鼠和裸鼠脾脏中的效应细胞为抗Thy + C抗性的非黏附淋巴细胞。这些结果与过继化学免疫疗法中的这种效应细胞为自然杀伤(NK)细胞相一致。然而,它们与经典NK细胞不同,因为它们在短期细胞毒活性(CRA)试验中在体外无直接细胞毒性,且在Winn试验中在体内不能中和肿瘤。