Jurincic-Winkler C D, von der Kammer H, Beuth J, Scheit K H, Klippel K F
Allgemeines Krankenhaus Celle, Urologische Klinik, Germany.
Anticancer Res. 1996 Jul-Aug;16(4A):2105-10.
The dynamics of specific KLH-antibody production after intracutaneous and intravesical instillation was analysed. Nine patients (male, n = 7; female, n = 2, mean age 68.6 years, range 47-75) with primary superficial carcinomas of the bladder were intracutaneously immunized with 1 mg Keyhole limpet hemocyanin (KLH) after the complete resection of the tumors. Treatment was continued for 6 consecutive weeks, monthly for one year and thereafter bimonthly for 2 subsequent years, consisting of 20 mg KLH in 20 ml saline introduced intravesically. The antibodies against KLH in patient sera were determined by means of a specially developed direct enzyme-linked immunosorbent assay (ELISA; according to H. von der Kammer, Max Planck Institute for Biophysical Chemistry, Goettingen, Germany). Blood was taken for antibody-titer examination before treatment and 8 weeks after treatment. The KLH-antibody titer increased significantly (Mann-Whitney-Test P = 0.02) after KLH therapy in bladder cancer patients, however the level varied considerably from patient to patient. 6 of 9 patients (67%) presented increased serum antibody titers to KLH after immunotherapy. 4 patients (44.4%) remained free of tumor during the established follow-up period of 10-45 months (median 30.7 months). One patient without increased antibody titer to KLH was free of tumor, 2 patients however, suffered from tumor recurrence after the KLH course. 2 patients presented with tumor recurrence in spite of increased antibody titers. No evidence of tumor progression occurred in patients with recurrence after KLH therapy. 4 of 5 patients (80%) without tumor recurrence presented with a positive skin test. Of patients with tumor recurrence, 50% had a negative skin test. 44.4% KLH-treated patients had tumor recurrence The recurrence rate was 1.6. The time to recurrence was 8.75 months. KLH instillation did not induce major side effects. Positive skin test reactivity and KLH antibody response were more commonly seen in responding patients (i.e. those who remained tumor free after therapy) than in non-responders. The production of KLH antibodies, apparently is the biological response to the antigen stimulus of KLH.
分析了皮内和膀胱内灌注后特异性钥孔戚血蓝蛋白（KLH）抗体产生的动力学。9例原发性浅表性膀胱癌患者（男性7例，女性2例，平均年龄68.6岁，范围47 - 75岁）在肿瘤完全切除后，皮内注射1mg钥孔戚血蓝蛋白（KLH）进行免疫。连续治疗6周，每月1次，持续1年，此后每2个月1次，持续2年，每次膀胱内注入20mg KLH溶于20ml生理盐水中。通过专门开发的直接酶联免疫吸附测定法（ELISA；根据德国哥廷根马克斯·普朗克生物物理化学研究所的H. von der Kammer方法）测定患者血清中抗KLH抗体。在治疗前和治疗后8周采集血液进行抗体滴度检测。膀胱癌患者接受KLH治疗后，KLH抗体滴度显著升高（曼 - 惠特尼检验P = = 0.02），然而患者之间的水平差异很大。9例患者中有6例（67%）免疫治疗后血清抗KLH抗体滴度升高。在10 - 45个月（中位30.7个月）的既定随访期内，4例患者（44.4%）无肿瘤复发。1例抗KLH抗体滴度未升高的患者无肿瘤复发，然而，2例患者在KLH疗程后出现肿瘤复发。2例患者尽管抗体滴度升高仍出现肿瘤复发。接受KLH治疗后复发的患者未出现肿瘤进展的证据。5例无肿瘤复发的患者中有4例（80%）皮肤试验呈阳性。肿瘤复发的患者中，50%皮肤试验呈阴性。44.4%接受KLH治疗的患者出现肿瘤复发。复发率为1.6。复发时间为8.75个月。KLH灌注未引起严重副作用。与无反应者相比，有反应的患者（即治疗后无肿瘤复发者）更常出现阳性皮肤试验反应和KLH抗体反应。KLH抗体的产生显然是对KLH抗原刺激的生物学反应。
