Interleukin-2 increases the antibody response in patients receiving autologous intralymphatic tumor cell vaccine immunotherapy.

Molecular biotherapy Pub Date : 1992-06-01
T W Williams, J M Yanagimoto, A Mazumder, C L Wiseman
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Abstract

The production of tumor-binding antibodies was studied in a group of cancer patients undergoing active specific immunotherapy with irradiated, cholesterol-treated, cell culture-derived autologous tumor cells injected by the intralymphatic route. Fifteen patients were analyzed: nine patients (four melanoma, one breast, one sarcoma, one colon, and one undifferentiated cancer) received three injections of 10 to 15 x 10(6) tumor cells, spaced 2 weeks apart, and six patients (two melanoma, two renal, one breast, and one colon cancer) received tumor cells admixed with 3 x 10(6) U recombinant interleukin-2 (IL-2) (Proleukin, Cetus, Emeryville, CA, USA) plus a 10-day intravenous infusion of 15 x 10(6) U/kg/day IL-2 after each immunization. Serum antibody binding to autologous tumor cells was measured at 2 and 4 weeks after initiation of therapy using an enzyme-linked immunosorbent assay with patient serum being added to adherent tumor cells bound to 96-well microtiter plates. After 4 weeks, we found a significant difference (0.02 less than P less than 0.04) in serum titer in the group receiving IL-2 (33% mean increase) compared with the non-IL-2 group (8% mean increase). Although neither group showed clinical improvement in response to the therapy, the results clearly demonstrated the efficacy of IL-2 in augmenting patient antibody response to autologous intralymphatic tumor cell immunization.

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白细胞介素-2增加了接受自体淋巴内肿瘤细胞疫苗免疫治疗的患者的抗体反应。
在一组接受主动特异性免疫治疗的癌症患者中,研究了肿瘤结合抗体的产生,这些患者使用经照射、胆固醇处理、细胞培养来源的自体肿瘤细胞,通过淋巴内途径注射。对15例患者进行分析:9例患者(4例黑色素瘤、1例乳腺癌、1例肉瘤、1例结肠癌和1例未分化癌)接受3次10至15 × 10(6)个肿瘤细胞注射,间隔2周,6例患者(2例黑色素瘤、2例肾癌、1例乳腺癌和1例结肠癌)接受肿瘤细胞与3 × 10(6) U重组白细胞介素-2 (IL-2) (Proleukin, Cetus, Emeryville, CA, USA)混合,每次免疫后再静脉输注15 × 10(6) U/kg/天IL-2。在治疗开始后2周和4周,使用酶联免疫吸附法测量与自体肿瘤细胞结合的血清抗体,将患者血清添加到附着在96孔微滴板上的肿瘤细胞中。4周后,我们发现IL-2治疗组血清滴度(平均升高33%)与非IL-2治疗组(平均升高8%)相比有显著差异(0.02 < P < 0.04)。尽管两组患者对该疗法的临床反应均没有改善,但结果清楚地表明IL-2在增强患者对自体淋巴内肿瘤细胞免疫的抗体反应方面的有效性。
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Innovation in science. Pretreatment natural killer antigen density correlates to clinical response in tumor patients receiving long-term subcutaneous recombinant interleukin-2 and recombinant interferon-alpha. The role of cytokines in tumor immunotherapy. Report on the 2nd Frankfurt International Cytokine Symposium 25-27 June 1992, Frankfurter Hof, Frankfurt, Germany. Relation between the biologic activities and chemical structures of synthetic microbial lipopeptide analogs in mice. Antitumor effect of recombinant human tumor necrosis factor-alpha analog combined with desmuramyl dipeptides LK-409 or LK-410 on sarcoma in mice.
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