Sedman P C, Ramsden C W, Brennan T G, Giles G R, Guillou P J
University Department of Surgery, St. James's University Hospital, Leeds, UK.
Br J Surg. 1988 Jun;75(6):591-4. doi: 10.1002/bjs.1800750633.
Adoptive cellular immunotherapy with lymphokine-(interleukin 2) activated killer (LAK) cells is not as successful in patients with gastrointestinal cancer as with other tumour types. This may be because the cytotoxic capacity of LAK cells from such patients is suboptimal. In this study we have sought to augment this activity by stimulating the lymphocytes with recombinant human interferon-gamma (r-HuIFN-gamma) in addition to interleukin 2 or by depleting the lymphocytes of adherent suppressive mononuclear cells. Both procedures augment LAK activity in gastrointestinal cancer patients but adherent cell depletion results in fewer cells being available for adoptive cellular immunotherapy. No further augmentation of LAK activity of adherent cell depleted cells could be accomplished by addition of r-HuIFN-gamma. Co-stimulation of unfractionated peripheral lymphocytes with r-HuIFN-gamma is the preferable procedure for the generation of LAK cells for adoptive cellular immunotherapy in patients suffering from gastrointestinal cancer.
采用淋巴因子(白细胞介素2)激活的杀伤细胞(LAK细胞)进行过继性细胞免疫治疗,在胃肠道癌患者中的效果不如在其他肿瘤类型患者中显著。这可能是因为这类患者的LAK细胞的细胞毒性能力欠佳。在本研究中,我们试图通过除白细胞介素2之外,还用重组人干扰素-γ(r-HuIFN-γ)刺激淋巴细胞,或者通过去除淋巴细胞中的黏附性抑制性单核细胞来增强这种活性。这两种方法都能增强胃肠道癌患者的LAK活性,但去除黏附细胞会导致可用于过继性细胞免疫治疗的细胞数量减少。通过添加r-HuIFN-γ,无法进一步增强去除黏附细胞后的细胞的LAK活性。对于患有胃肠道癌的患者,用r-HuIFN-γ共同刺激未分级的外周淋巴细胞是生成用于过继性细胞免疫治疗的LAK细胞的优选方法。