体外淋巴细胞对自体黑色素瘤的反应:设计新的过继免疫治疗方案的线索。

G Parmiani, L Rivoltini
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引用次数: 0

摘要

最近的研究表明,暴露于重组白细胞介素-2 (il -2)后,在体外和体内可以产生不同类型的抗肿瘤淋巴细胞(T和非T)。在体外,利用抗CD3单克隆抗体和il -2选择性扩增CD3细胞是可能的。粘附可以选择具有较高裂解活性的淋巴因子激活杀伤细胞(LAK)的一小部分亚群。我们已经研究了是否可以获得黑色素瘤特异性t淋巴细胞用于治疗或通过适当使用有限量的il -2在体内内源性扩增。从肿瘤病变或血液中获得的淋巴细胞克隆分析表明存在黑色素瘤限制性t淋巴细胞,它们具有细胞毒性或辅助功能。虽然是少数,但在自体黑色素瘤和b细胞存在的情况下,这些细胞可以在低量的rIL-2 (3-30 Cetus U/ml)下产生和扩增。在t淋巴细胞生长的某些阶段使用rIL-1和rIL-4,以及rIL-2,可以帮助更有选择性地扩大黑色素瘤特异性细胞。这些t细胞是主要的组织相容性复合体,它们的杀伤受到限制,但它们也需要看到靶细胞上的粘附分子(ICAM-1)。因此,在这些结果的基础上可以设想新的临床方案。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
In vitro lymphocyte response to autologous melanoma: clues in designing new adoptive immunotherapy protocols.

Recent studies indicate that different types of antitumour lymphocytes (T and non-T) can be generated in vitro and in vivo after exposure to recombinant interleukin-2 (rIL-2). In vitro it is possible to selectively expand the CD3 cells by using anti-CD3 monoclonal antibody and rIL-2. Adherence can select a minor subpopulation of lymphokine-activated killer (LAK) cells (A-LAK) endowed with a higher lytic activity. We have investigated whether melanoma-specific T-lymphocytes can be obtained to be used for therapy or endogenously expanded in vivo by the appropriate use of limited amounts of rIL-2. Clonal analysis of lymphocytes obtained either from tumour lesions or from blood indicated the existence of melanoma-restricted T-lymphocytes, both with cytotoxic or helper function. Though a minority, these cells can be generated and expanded with low amounts of rIL-2 (3-30 Cetus U/ml) in the presence of autologous melanoma and B-cells. The use of rIL-1 and rIL-4, together with rIL-2 at certain phases of T-lymphocyte growth, can help in expanding more selectively the melanoma-specific cells. These T-cells are major histocompatibility complex-restricted in their killing but they also need to see adhesion molecules (ICAM-1) on the target cells. New clinical protocols can thus be conceived on the basis of some of these results.

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