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[淋巴因子激活的杀伤细胞与癌症免疫疗法]

[LAK cells and immunotherapy of cancer].

作者信息

Khayat D, Weil M, Soubrane C, Jacquillat C

机构信息

Laboratoire du Service d'oncologie médicale, Hôpital de la Salpêtrière, Paris, France.

出版信息

Bull Cancer. 1988;75(1):3-7.

PMID:3258774
Abstract

Cancer immunotherapy still appears very unsatisfactory in humans. However, it has been shown recently that Interleukin 2 (IL2) could be used to generate, in vitro as well as in vivo, a new anti-tumoral activity directed against fresh tumor cells, allogenic as well as autologous, both of leukemic and solid tumor origin. This activity is not connected with the NK activity, but with a lymphocyte sub-population termed 'Lymphokine Activated Killer (LAK) Cells'. The exact nature of these LAK cell precursors is still a matter of controversy: 'nul' lymphocyte, T or NK markers bearing lymphocytes, or different precursors according to the system of activation that has been used. However, after being activation, these LAK cells always express T cell-markers. The activation has a very short lifespan, explaining the need for a prolonged contact of the cells with IL2, and therefore the necessity to continue injecting the lymphokine in vivo. The clinical results that have been reported so far are still very preliminary. The most common treatment protocol consists of 5 days of IL2 injections followed by 5 days of leukapheresis and in vitro activation of the collected cells, and then auto-transfusion of the activated cells and IL2 during the next 5 days. The clinical toxicity encountered is impressive in terms of frequency as well as severity. Clinical activity seems to be relatively weak. Nevertheless, the concept still appears to be very promising.

摘要

癌症免疫疗法在人体中的效果仍然很不理想。然而,最近有研究表明,白细胞介素2(IL2)可用于在体外和体内产生一种针对新鲜肿瘤细胞的新的抗肿瘤活性,这些肿瘤细胞包括同种异体和自体的,既有白血病起源的,也有实体瘤起源的。这种活性与自然杀伤(NK)活性无关,而是与一种称为“淋巴因子激活的杀伤细胞(LAK细胞)”的淋巴细胞亚群有关。这些LAK细胞前体的确切性质仍存在争议:是“裸”淋巴细胞、带有T或NK标记的淋巴细胞,还是根据所使用的激活系统而有所不同的前体。然而,在被激活后,这些LAK细胞总是表达T细胞标记。激活的寿命非常短,这就解释了为什么细胞需要与IL2长时间接触,因此有必要在体内持续注射这种淋巴因子。目前报道的临床结果仍然非常初步。最常见的治疗方案包括连续5天注射IL2,随后进行5天的白细胞分离术,并在体外激活收集到的细胞,然后在接下来的5天内将激活的细胞和IL2自体回输。所遇到的临床毒性在频率和严重程度方面都令人印象深刻。临床活性似乎相对较弱。尽管如此,这一概念似乎仍然非常有前景。

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