CD3AK细胞和LAK细胞治疗晚期恶性肿瘤的临床和实验研究

将５１例晚期恶性肿瘤患者（男性２３例，女性２８例）分成两组，其中一组（３１例）以ＣＤ３ＭｃＡｂ（ＣＤ３单克隆抗体）和小剂量ＩＬ－２（５００ｕ／ｍｌ）共同诱导的ＣＤ３ＡＫ细胞治疗，另一组（２０例）输注大剂量ＩＬ－２（１０００ｕ／ｍｌ）诱导的常规ＬＡＫ细胞治疗，以探讨降低ＩＬ－２用量、提高杀伤细胞细胞毒活性的可能性。结果显示ＣＤ３ＡＫ组患者生活质量改善、症状缓解均优于ＬＡＫ组。ＣＤ３ＡＫ组ＰＲ＋ＭＲ率较ＬＡＫ组高２９．０％，Ｓ＋Ｐ率和死亡率分别较ＬＡＫ组低１２．４％和９．６％。同时比较了ＣＤ３ＡＫ细胞与ＬＡＫ细胞的体外增殖和细胞毒活性，结果表明ＣＤ３ＡＫ细胞增殖率高于ＬＡＫ细胞（Ｐ＜０．０１），靶细胞抑制率二者在０．０５水平无显著差异。提示ＣＤ３ＭｃＡｂ在刺激杀伤细胞活性，尤其在提高其增殖能力方面，具有显著的作用，ＣＤ３ＡＫ／ＩＬ－２能更有效地治疗晚期恶性肿瘤。     

低剂量IL-2诱导的人胚胎脾脏CD_3AK细胞治疗晚期恶性肿瘤效果及实验研究

用ＣＤ３ＭｃＡｂ和低剂量ＩＬ－２（５００Ｕ／ｍｌ）诱导的人胎脾ＣＤ３ＡＫ细胞治疗４３例晚期恶性肿瘤患者，取得疗效。经２～８疗程治疗，多数患者症状缓解，生活质量改善，ＰＲ＋ＭＲ１８例（４１．９％），Ｓ＋Ｐ２５例（５８．１％），死亡９例（２０．９％）。全组无严重毒副反应发生。同时比较ＣＤ３ＡＫ细胞和常规ＬＡＫ细胞体外增殖及其杀伤活性，表明前者１４４ｈ增殖力高于后者（Ｐ＜０．０１），靶细胞抑制率二者无显著差异（Ｐ＞０．０５）。初步表明ＣＤ３ＡＫ／ＩＬ－２疗法效果肯定，毒副作用小，可能成为继ＬＡＫ／ＩＬ－２之后更为有效的肿瘤辅助治疗。     

NK和sIL-2R在肺癌化疗中的临床价值

为了评价肺癌患者化疗后血清ＮＫ细胞活性及ｓＩＬ－２Ｒ水平变化的临床价值，作者采用ＬＤＨ释放法和双抗体夹心ＥＬＩＳＡ法检测４７例肺癌病人和４１例正常对照者的血清ＮＫ细胞活性和ｓＩＬ－２Ｒ水平。结果显示，与正常人相比，肺癌病人血清ｓＩＬ－２Ｒ水平增高（Ｐ＜０．０１），ＮＫ细胞活性降低（Ｐ＜０．０５），且化疗后有效病人血清ｓＩＬ－２Ｒ水平明显低于化疗前（Ｐ＜０．０１）。结果提示血清ＮＫ细胞活性和ｓＩＬ－２Ｒ水平可以作为判断肺癌疗效和预后的指标。     

LICC细胞和LAK细胞治疗晚期恶性肿瘤的疗效观察

采用淋巴因子诱导的细胞毒细胞（ＬＩＣＣ）和ＩＬ—２／ＬＡＫ细胞治疗３２例晚期恶性肿瘤患者，ＬＩＣＣ治疗２０例，ＩＬ—２／ＬＡＫ治疗１２例，结果发现６８．８％（２２／３２）卡氏得分上升，多数患者癌性症状减轻，生活质量提高，以ＬＩＣＣ组优于ＬＡＫ组，ＣＲ＋ＰＲ＋ＭＲ率，ＬＩＣＣ为４０．０％（１２／２０），ＬＡＫ组为１６．７％（２／１２）。作者认为过继免疫作为一种癌症辅助治疗方法应予肯定；ＬＩＣＣ治疗安全、副反应小，抗瘤谱广，费用低，疗效优于ＩＬ—２／ＬＡＫ，值得扩大应用性研究。     

原发性肝癌肝动脉化疗栓塞合并LAK/IL-2灌注治疗的临床Ⅲ期观察

评价肝动脉化疗栓塞合并ＬＡＫ／ＩＬ┐２灌注治疗原发性肝癌的初步疗效。方法不能切除的肝癌患者经肝动脉化疗栓塞后灌注自体ＬＡＫ细胞及ＩＬ┐２，并与单独行肝动脉化疗栓塞的不能切除肝癌患者比较其肿瘤大小，生活质量的变化及毒副反应。结果经肝动脉化疗栓塞合并ＬＡＫ／ＩＬ┐２灌注治疗的２２例肝癌有效率（ＣＲ＋ＰＲ）为１３．６％，包括１例完全缓解和２例部分缓解，而单独化疗栓塞对照组１７例中仅１例显示部分缓解（有效率５．９％）。化疗栓塞＋ＬＡＫ／ＩＬ┐２治疗组与单独化疗栓塞对照组中ＭＲ、ＳＤ、ＰＤ分别为５、１２、１例和１、１１、４例。治疗组中大多数病人生活质量改善或稳定，而对照组中生活质量则无提高。两组病人的毒副反应均较轻而短暂。结论经肝动脉化疗栓塞合并ＬＡＫ／ＩＬ┐２灌注治疗原发性肝癌疗效较优于单独肝动脉化疗栓塞治疗，原发性肝癌更有效的综合治疗方案有待进一步探索     

枸杞多糖联合LAK／IL—2疗法对75例晚期肿瘤的疗效观察

用枸杞多糖（ＬＢＰ）联合ＬＡＫ／ＩＬ－２疗法临床试验治疗７９例晚期肿瘤患者，其中７５例可评估病人资料分析提示，ＬＢＰ联合ＬＡＫ／ＩＬ－２疗法组疗效（４０．９％）显著优于ＬＡＫ／ＩＬ－２疗法组（１６．１％）。两种治疗方案对恶性黑色素瘤、肾癌、直结肠癌、肺癌、恶性胸水和鼻咽癌有一定的疗效。ＬＢＰ联合ＬＡＫ／ＩＬ－２治疗组的缓解持续时间显著长于ＬＡＫ／ＩＬ－２治疗组。ＬＢＰ联合ＬＡＫ／ＩＬ－２治疗组治疗     

急性白血病患者血清可溶性白细胞介素2受体测定及其临床意义

测定９８例急性白血病（ＡＬ）患者血清可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）水平，各型ＡＬ患者ｓＩＬ－２Ｒ均明显升高，且ＡＬＬ〉Ｍ５〉Ｍ２〉Ｍ３。ｓＩＬ－２Ｒ水平与骨髓中原始细胞数、外周白血细胞数、外周成熟淋巴细胞绝对值无关。动态观察发现化疗后不能获得完全缓解（ＣＲ）患者治疗前ｓＩＬ－２Ｒ明显高于获得ＣＲ患者。各型ＡＬ患者化疗ＣＲ后，ｓＩＬ－２Ｒ水平较治疗前均明显下降，除急性淋巴细胞白血病外，Ｍ２、     

枸杞多糖联合LAK／IL－2疗法对75例晚期肿瘤的疗效观察

用枸杞多糖（ＬｙｃｉｕｍＢａｒｂａｒｕｍＰｏｌｙｓａｃｃｈａｒｉｄｅｓ，ＬＢＰ）联合ＬＡＫ／ＩＬ－２疗法临床试验治疗７９例晚期肿瘤患者，其中７５例可评估病人资料分析提示，ＬＢＰ联合ＬＡＫ／ＩＬ－２疗法组疗效（４０．９％）显著优于ＬＡＫ／ＩＬ－２疗法组（１６．１％）。两种治疗方案对恶性黑色素瘤、肾癌、直结肠癌、肺癌、恶性胸水和鼻咽癌有一定的疗效。ＬＢＰ联合ＬＡＫ／ＩＬ－２治疗组的缓解持续时间显著长于ＬＡＫ／ＩＬ－２治疗组。ＬＢＰ联合ＬＡＫ／ＩＬ－２治疗组治疗前后外周血淋巴细胞（ＰＢＬ）的ＮＫ、ＬＡＫ活性增高程度均显著大于ＬＡＫ／ＩＬ－２治疗组，说明ＬＢＰ能够提高ＬＡＫ／ＩＬ－２疗法对晚期肿瘤的治疗效果。     

低剂量IL—2诱导的人胚胎脾脏CD3AK细胞治疗晚期恶性肿瘤效果及…

用ＣＤ３ＭｃＡｂ和低剂量ＩＬ－２诱导的人胎脾ＣＤ３ＡＫ细胞治疗４３例晚期恶性肿瘤患者，取得疗效。经２－８疗程治疗，多数患者症状缓解，生活改善，ＰＲ＋ＭＲ１８例，Ｓ＋Ｐ２５雎，死亡９例。全组无严重毒副反应发生。同时比较ＣＤＡＫ细胞和常规ＬＡＫ细胞体外增殖及其杀伤活性，表明前者１４４ｈ增殖力高于后者，靶细胞抑制率二者无显著差异。     

应用人胎儿脾LAK细胞治疗62例晚期恶性肿瘤病人的疗效观察

采用人胎儿脾ＬＡＫ细胞治疗６２例晚期恶性肿瘤病人。结果表明人胎儿脾ＬＡＫ细胞的临床应用安全可行，多数病人在治疗期间一般状况得到改善。总缓解率为（ＰＲ）２２．５８％，平均缓解时间为１５．９５个月。缓解率与克氏评分和接受４次疗程的ＩＬ－２／ＬＡＫ细胞用量有关。在１８．４个月的治疗期间，死亡率为２０．９７％，平均生存期为１６．５０个月。ＩＬ－２／ＬＡＫ细胞对肾癌、黑色素瘤、结肠癌、肺癌和肝癌的转移灶有较好疗效，对原发灶也有一定作用。     

Enhanced antimetastatic activity of lymphokine-activated killer cells purified and expanded by their adherence to plastic

We have recently reported a simple and reproducible technique for the purification and rapid expansion of homogeneous populations of large granular lymphocytes expressing a natural killer cell phenotype and high levels of broad antitumor cytotoxic activity [lymphokine-activated killer (LAK) activity]. This technique exploits the observation that, in the presence of recombinant interleukin 2 (rIL-2), large granular lymphocytes/natural killer cells become adherent to plastic surfaces, actively proliferate, and acquire high levels of LAK activity. Because of their adherent properties these cells have been termed adherent LAK or A-LAK cells. The present studies investigate the antimetastatic effects of A-LAK cells in a syngeneic rat model of experimental pulmonary and hepatic metastases. For pulmonary metastases, F344 rats received i.v. injections with a natural killer-resistant mammary adenocarcinoma, MADB106, and, for hepatic metastases, animals received an intrasplenic injection of MADB106 tumor cells followed by surgical splenectomy. Three days later, the animals were treated with A-LAK cells alone, A-LAK cells plus rIL-2, or rIL-2 alone. These treatments were compared to immunotherapy using standard cultures of LAK cells (unfractionated spleen cells) and rIL-2. The results indicate that the administration of unfractionated LAK cells plus interleukin 2 (IL-2) was effective in reducing established lung or liver metastases in this rat model. However, the results also indicate that purified populations of A-LAK cells in combination with rIL-2 demonstrate dramatic and superior antimetastatic effects when compared to LAK cells cultured under standard conditions. The antimetastatic effects of standard LAK cells or A-LAK cells plus IL-2 translated into significant survival benefits compared to animals receiving no therapy or IL-2 therapy alone. Survival after therapy with A-LAK cells plus IL-2 was significantly prolonged compared to treatment with standard LAK cells. These data suggest that purified populations of LAK cells (derived from natural killer cells) may prove superior for adoptive immunotherapy in the clinical setting.     

A randomized phase II trial of continuous infusion interleukin-2 or bolus injection interleukin-2 plus lymphokine-activated killer cells for advanced renal cell carcinoma.

PURPOSE: Since 1985, multiple centers have demonstrated that interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells produce durable anticancer responses in patients with metastatic renal cell carcinoma. High-dose recombinant IL-2 (rIL-2) has been administered by intravenous bolus injection (Rosenberg SA, et al: N Engl J Med 313:1485-1492, 1985) and by continuous intravenous infusion (West WH, et al: N Engl J Med 316:898-905, 1987) combined with lymphokine-activated killer (LAK) cells, with both methods producing responses in patients with advanced renal cell carcinoma. The Extramural IL-2/LAK Working Group has conducted a randomized phase II trial of two intravenous high-dose rIL-2 regimens (bolus three times daily or 24-hour continuous infusion) to determine if either one manifests greater anticancer activity or a more acceptable toxicity profile. PATIENTS AND METHODS: Ninety-four patients with measurable advanced renal cell carcinoma were enrolled on this study: 46 to the bolus injection arm and 48 to the continuous infusion arm. On both arms, patients underwent a priming phase of rIL-2 administration, four daily lymphocytaphereses to harvest mononuclear cells that were placed in 3- to 4-day culture for generation of LAK cells, and an rIL-2/LAK coadministration phase. Patients were then observed monthly for evidence of response to this therapy and were offered up to two additional courses of treatment every 3 months if evidence of response was detected. RESULTS: Twenty percent of patients on the bolus injection arm experienced objective responses (three complete responses and six partial responses); 15% of patients on the continuous infusion arm responded (two complete responses and five partial responses). Complete responses were durable, persisting for 310+ to 700+ days. The incidence of severe life-threatening toxicities typical of high-dose rIL-2 therapy was similar in both arms (eg, patients with hypotension requiring pressors: bolus 71%, continuous 63%; oliguria less than or equal to 200 mL/8 hours: bolus 65%, continuous 71%). More episodes of fever, infection, and serum alkaline phosphatase elevation were associated with the continuous infusion arm, while more thrombocytopenia occurred on the bolus injection arm. Four patients (three bolus injection, one continuous infusion) died of respiratory and circulatory failure while under treatment. No clinical or laboratory parameter accompanying treatment on either arm was, by univariate or multivariate analysis, associated with an increased likelihood of response. CONCLUSIONS: Both methods of high-dose rIL-2/LAK cell administration produce nearly equivalent anticancer activity and toxicity in the treatment of renal cell carcinoma. The ability to predict responding patients based on patient or treatment characteristics is not possible.     

Phase I trial of intraperitoneal recombinant interleukin-2/lymphokine-activated killer cells in patients with ovarian cancer

Ten patients with ovarian cancer refractory to conventional therapy were treated with intraperitoneal (i.p.) recombinant interleukin-2 (rIL-2) and lymphokine-activated killer cells (LAK). The 28-day protocol consisted of 6 priming i.p. rIL-2 infusions on days 0, 4, 6, 8, 10, and 12. Leukapheresis was performed for mononuclear cell collection on days 15, 16, 17, and 18 and lymphokine-activated killer cells were given i.p. with the rIL-2 on days 19 and 21. Three additional i.p. rIL-2 infusions were given on days 23, 25, and 27. Three dose levels of rIL-2 were tested: 5 X 10(5), 2 X 10(6), and 8 X 10(6) units/m2 body surface area. The dose-limiting toxicity was abdominal pain secondary to ascites accumulation with significant weight gain. Other toxic effects included decreased performance status, fever, nausea and vomiting, diarrhea, and anemia. Peripheral lymphocytosis and eosinophilia were seen at all dose levels. The maximum tolerated dose is 8 X 10(6) units/m2/dose. Peripheral and peritoneal IL-2 levels were measured with a bioassay using an IL-2-dependent cell line. At the highest dose level, serum IL-2 was greater than 10 units/ml for 18 h. After the first infusion, a 2-log dilution of the i.p. IL-2 was measured in the serum. In the postleukapheresis i.p. IL-2-dosing period less IL-2 was detected in the serum than in the earlier i.p. IL-2-priming period. The induction and persistence of LAK activity were studied. Peritoneal LAK activity was detected as early as 4 days after the first i.p. infusion, by day 11 in all evaluable patients, and persisted for the 6-day interval between priming IL-2 and LAK/IL-2 infusion. Peritoneal lytic activity persisted until day 28 in 5 tested patients. These peritoneal cells retained lytic activity 48 h in culture medium without rIL-2 present. Peritoneal LAK activity correlated with the percentage of mononuclear cells and the percentage of CD56-positive mononuclear cells in the peritoneum. The yield of peripheral lymphocytes after the six i.p. priming doses of rIL-2 correlated with the dose level of rIL-2 infused. Peripheral blood LAK activity showed a minimal, however progressive, increase during the treatment protocol. LAK activity could be enhanced if rIL-2 was present during the 4-h assay. These studies indicate that i.p. rIL-2 infusion induced durable regional LAK activity and primes peripheral blood cells for LAK activity if exposed briefly to additional IL-2.     

Lymphokine-activated killer cells in rats: analysis of progenitor and effector cell phenotype and relationship to natural killer cells

The progenitor and effector cell phenotype of lymphokine-activated killer (LAK) cells generated in F344 rats by recombinant human interleukin 2 (IL-2) (rIL-2) were analyzed. Highly purified populations of peripheral blood large granular lymphocytes (LGL) exhaustively depleted of T-cells were fully capable of generating high levels of LAK activity by 3 to 5 days in culture while purified populations of resting T-cells devoid of LGL could not generate LAK activity. This pure population of LGL expressed surface markers characteristic of rat natural killer (NK) cells [i.e., OX8+, asialomonoganglioside (asialo-GM1+), laminin+, OX19-, R1-3B3-, W3/25-, Ia-, surface immunoglobulin negative (SIg-)]. Further evidence that NK cells were the progenitors of cells with LAK activity was obtained by treatment of spleen or peripheral blood lymphocytes with anti-laminin or anti-asialo-GM1 antibodies plus complement or with the lysosomotropic agent L-leucine methyl ester. These treatments effectively depleted LGL/NK cell activity and the subsequent generation of rIL-2-induced LAK activity. Analysis of the LAK effector phenotype by cell sorting demonstrated that the majority of cells with LAK activity were OX8+, asialo-GM1+, laminin+, OX6+, OX19-, R1-3B3-, W3/25-, and SIg-. Furthermore, treatment of LAK cells with L-leucine methyl ester also significantly reduced their cytolytic activity. Thus, the LAK effector cells were also LGL and expressed surface marker characteristic of activated NK cells and not those of mature T- or B-cells. The proliferative response of rat spleen or blood lymphocytes to rIL-2 appeared to be primarily associated with LGL/NK cells since depletion of NK cells by anti-asialo-GM1 or anti-laminin antibody plus complement or by L-leucine methyl ester significantly (P less than 0.001) reduced the incorporation of [3H]thymidine into DNA. In contrast, depletion of T-cells (by anti-T-cell antibody plus complement) did not significantly affect rIL-2-induced proliferation. Similarly, T-cell-depleted, highly purified populations of LGL gave substantial proliferative responses to rIL-2. These studies clearly indicate that in the rat, the major cell population activated by rIL-2 is the LGL/NK cell and these cells appear to represent the major population of cells in blood or spleen which generate broad antitumor (LAK) cytotoxicity.     

晚期肺癌癌性胸水的免疫治疗

Ten patients with advanced lung cancer complicated by malignant pleural effusion were treated by intrapleural transfer of autologous LAK cells induced from lymphocytes of malignant effusions in the presence of rIL-2 and by administration of rIL-2 10 days before and after the transfer of LAK cells. The pleural effusions disappeared in 8 patients and significantly reduced in the other two. The number of tumor cells in the pleural effusion was obviously decreased while the number of lymphocytes was significantly increased. No changes were found in 4 responders during 4 months follow-up after treatment. No serious side effects were observed in all these 10 patients. The results indicated that transfer of LAK cells combined with rIL-2 in the treatment of patients with malignant pleural effusion due to advanced lung cancer is effective, safe and feasible.     

Effects of Recombinant Interferon-Gamma and Interleukin-2 on the Generation of Lymphokine-Activated Killer Cells in Vitro

In order to determine if recombinant interferon-γ (rIFN-γ) can augment the effect of recombinant interleukin-2 (rIL-2) in generating lymphokine-activated killer (LAK) cells, we have incubated normal peripheral blood mononuclear cells (PBMC) with these lymphokines for 3 days and then tested their LAK and natural killer (NK) cell activity. We have found that LAK activity in PBMC from 13 out of 13 normal donors was increased by the combined lymphokines above that due to either lymphokine alone, provided that rIL-2 was present at suboptimal concentration: Optimal levels of rIFN-γ (100 U/ml) were able to enhance the LAK-inducing activity of suboptimal levels (5 U/ml) but not optimal levels (100 U/ml) of rIL-2. NK activity showed a similar response to these concentrations of lymphokines. Activation of LAK/NK cells was accompanied by increases in the percentages of Leu 19⁺ (CD56) cells and TAC⁺ (IL-2-receptor) cells, and in the intensity of TAC antigen expression. These results indicate that combination rIFN-γ and rIL-2 may be more effective in generating LAK/NK cells than rIL-2 alone, particularly with suboptimal concentrations of rIL-2 such as occur during continuous infusion therapy with this agent.     

Identification of a novel CD56- lymphokine-activated killer cell precursor in cancer patients receiving recombinant interleukin 2.

Circulating lymphokine-activated killer (LAK) cell activity in cancer patients receiving recombinant interleukin 2 (rIL-2) therapy is confined to cells expressing the CD56- surface marker. However, CD56- cells from these patients but not normal individuals have been reported to exhibit LAK cytotoxicity only following in vitro activation with rIL-2. Studies were performed to document the existence of CD56- LAK precursor cells and to phenotypically characterize this population in patients receiving rIL-2 therapy using fluorescence-activated cell sorter-purified CD56- cell subsets. Initial studies confirmed that CD56- cells exhibit NK activity [20 +/- 7 (SE) LU/10(6) cells] but not LAK activity (0 +/- 0 LU/10(6) cells) when evaluated directly from peripheral blood of patients receiving rIL-2. CD56- cells from patients but not normal individuals developed significant LAK cytolytic activity against NK-resistant COLO 205 targets (16 +/- 3 LU/10(6) cells) when cultured for 3 days with 1500 units/ml rIL-2. The CD56- LAK precursor activity was confined to cells expressing a CD56-CD16+ phenotype and a large granular lymphocyte morphology; little or no NK or LAK precursor activity was detectable in CD56-CD5+ T-cells from patients. Phenotypic characterization of CD16+CD56- cells revealed that this population is uniformly CD11a+,CD18+, and CD38+ and is heterogeneous in its expression of CD11b, CD11c, and CD16/Leu 11c. These results indicate that rIL-2 administration induces enhanced LAK precursor activity in a novel population of CD5-CD16+CD56- cells.     

Lymphokine-activated killer cells in rats: analysis of tissue and strain distribution, ontogeny, and target specificity

The coculture of lymphoid cells from Fischer 344 rats with recombinant human interleukin 2 (rIL-2) resulted in the generation of lymphokine-activated killer (LAK) cells. Maximal LAK activity was obtained between 200 and 1000 units/ml rIL-2. Lymphoid cells from spleen, thymus, bone marrow, peripheral blood, and lymph nodes were able to generate LAK activity although the kinetics and magnitudes of the responses were appreciably different among these tissues. Thus, while spleen and blood lymphocytes responded quickly (by day 3) and gave the highest level of LAK activity in response to rIL-2, bone marrow and thymus cells responded only by 7 to 9 days in culture. LAK activity could be generated from a variety of rat strains regardless of whether there were high or low levels of endogenous splenic natural killer (NK) activity, but the early (day 3) response was lower in the strains with low levels of NK activity. Cells with LAK activity could lyse a variety of tumor targets including fresh ascites or fresh syngeneic solid tumor explants but could not lyse fresh normal cells including syngeneic fibroblasts, peripheral blood lymphocytes, bone marrow cells, thymocytes, or T,B blasts. The generation of LAK activity required a concomitant proliferative response and could be completely abrogated by mitomycin C, actinomycin D, or X-irradiation above 500 rads. These treatments, however, did not affect natural killer activity or short-term (4 h) IL-2-boosted NK activity. LAK activity could be generated from spleen cells obtained from rats as early as 10 days of age but could not be generated from unfractionated neonatal spleen, neonatal liver, or peritoneal macrophages. The ontogeny of the development of splenic LAK activity correlated closely to the development of concurrent natural killer activity. When mixed with an NK-resistant mammary adenocarcinoma (MADB106) and adoptively transferred to normal syngeneic recipients in standard Winn-type assays, LAK cells were effective at inducing complete tumor inhibition.     

经支气管动脉输注LAK／IL－2治疗肺癌的免疫指标变化及临床意义

５４例原发性肺癌患者经支气管动脉输注ＬＡＫ／ＩＬ－２前后分别测定了体内ＮＫ活性、淋转、Ｔ细胞亚群及体液免疫指标的变化。结果表明，治疗前体内ＮＫ、淋转、ＯＫＴ３、ＯＫＴ４均低于正常值，ＯＫＴ８、Ｃ３、ＩｇＡ、ＩｇＭ治疗前均高于正常值，治疗后大部分观察指标趋于正常。     

Ewing's sarcoma: ex vivo sensitivity towards natural and lymphokine-activated killing

We studied the ex vivo cell-mediated cytotoxicity of natural killer (NK) and lymphokine-activated killer (LAK) cells against continuously cultured Ewing's sarcoma cells from 3 different patients. Target cell lysis was measured in a 4-hour 51Cr radioisotope release assay. At an effector to target (E:T) ratio of 50:1, the mean (+/- 1 SD) cytolysis by fresh purified large granular lymphocytes (NK cells) was 20 +/- 8, 25 +/- 2, and 21 +/- 3% in Ewing's sarcoma cell lines 6647, 5838, and A4573, respectively. Under identical conditions, NK cells lysed 56 +/- 7% of K562 (a standard NK target), and 3 +/- 3% of Daudi (a standard NK-resistant LAK target). When compared to fresh unseparated peripheral blood mononuclear cells (PBMC), purified NK cells did not exhibit an enhanced cytotoxic reactivity against either Ewing's sarcoma target. In contrast, LAK cells (i.e., PBMC that were preincubated for 4 days in the presence of rIL-2) were highly cytotoxic against all three Ewing's sarcoma targets. LAK activity was dependent on the concentration of rIL-2 used in PBMC cultures. Optimum cell-mediated toxicity against the standard LAK target Daudi (99 +/- 10% cytolysis at 50:1 E:T ratio) was achieved at rIL-2 concentrations of 1,000 u/ml. LAK cells grown under these conditions were also effective against Ewing's sarcoma cells. At an E:T ratio of 50:1, 86 +/- 16, 85 +/- 16, and 67 +/- 13% inhibition was observed in 6647, 5838, and A4573 cells, respectively, as compared to 17 +/- 10, 19 +/- 15, and 29 +/- 11% cytolysis by fresh uninduced PBMC. In summary, our results suggest that rIL-2-induced LAK-type immune effector cells may be of some therapeutic value in the treatment of poor prognosis Ewing's sarcoma.