Lucci J A, Manetta A, Cappuccini F, Ininns E K, Dett C A, DiSaia P, Yamamoto R S, Berman M L, Soopikian J, Granger G A
Department of Obstetrics and Gynecology, University of California, Irvine 92717.
Gynecol Oncol. 1992 May;45(2):129-35. doi: 10.1016/0090-8258(92)90274-m.
We examined the in vitro sensitivity of continuous ovarian cancer cells to lymphokine-activated killer T cells (T-LAK) alone or in combination with cytokines. Lymphocyte viability in T-LAK cultures generated from normal donors and ovarian cancer patients declined in the first 2 to 4 days; however, the remaining cells in these cultures maintained a constant rate of proliferation for long periods in vitro. These cells became 90-95% CD3+ TCR+ -alpha/beta T-cells after 7-10 days in culture. The T-LAK cells from normal donors and cancer patients expressed an equal ability to induce lysis of a panel of human target cells (NK-sensitive K562, NK-insensitive RAJI, and two human ovarian tumor lines, SKOV-3 and OVCAR-3), demonstrating that they are nongenetically restricted killers. Preincubation of either the effector or target cells with tumor necrosis factor or interferon-gamma or addition of these cytokines directly to cytolytic assays did not alter the degree of cell lysis in vitro. This is a method for generating large numbers of autologous, cytolytically active T-LAK cells from the blood of ovarian cancer patients that could be employed in adoptive intraperitoneal immunotherapy.
我们研究了持续性卵巢癌细胞对单独的淋巴因子激活的杀伤性T细胞(T-LAK)或与细胞因子联合使用时的体外敏感性。从正常供体和卵巢癌患者中产生的T-LAK培养物中的淋巴细胞活力在前2至4天下降;然而,这些培养物中剩余的细胞在体外长时间保持恒定的增殖速率。培养7至10天后,这些细胞变成90-95%的CD3+ TCR+ -α/β T细胞。来自正常供体和癌症患者的T-LAK细胞表现出同等能力诱导一组人类靶细胞(NK敏感的K562、NK不敏感的RAJI以及两个人类卵巢肿瘤细胞系SKOV-3和OVCAR-3)的裂解,表明它们是不受基因限制的杀伤细胞。用肿瘤坏死因子或干扰素-γ对效应细胞或靶细胞进行预孵育,或将这些细胞因子直接添加到细胞溶解试验中,均未改变体外细胞裂解的程度。这是一种从卵巢癌患者血液中产生大量自体、具有细胞溶解活性的T-LAK细胞的方法,可用于过继性腹腔内免疫治疗。