Winters W D, Lamm D L
Cancer Res. 1981 Jul;41(7):2672-6.
Levels of serum antibody to Bacillus Calmette-Guérin (BCG) were determined by solid-phase radioimmunoassays in 48 normal donors and 60 patients with bladder cancer. Of 57 patients enrolled in a randomized prospective controlled trial of BCG immunotherapy, 47 were followed for up to 30 months, thus permitting comparisons of tumor recurrence, delayed cutaneous hypersensitivity responses to purified protein derivative (PPD), and serum BCG antibody levels at specific intervals during the clinical course. Sera from normal donors and cancer patients prior to BCG therapy had equally low levels of BCG antibody. AFter administration of intravesical and percutaneous BCG, significant rises of serum BCG antibody levels were detected in 23 of 24 randomized BCG immunotherapy patients. Skin test responses to PPD and serum BCG antibody levels had a close correlation as immune response indicators in 14 of 24 BCG therapy patients, while rises in serum BCG antibody levels were a better response indicator than PPD skin test reactions in the other 10 patients. Eleven of the 23 patients randomized into the non-BCG treatment group had tumor recurrence, although tumors recurred in only six of the 24 randomized patients in the BCG therapy group. Two additional nonrandomized BCG-treated patients had tumor recurrence. All eight BCG-treated patients with tumor recurrence had documented increases in serum BCG antibody levels after BCG therapy. Only three of these eight patients had conversion of PPD skin test responses from negative to positive; three were positive before immunotherapy and two remained negative after BCG therapy. Levels of antibodies reactive with human adenovirus type 5 and with Escherichia coli antigens were similar in sera from normal donors and from the randomized bladder cancer patients in both the BCG and non-BCG treatment groups. These results suggest that serum BCG antibody responses are as useful as PPD skin tests in identifying immunological responses to the immunoadjuvant BCG during immunotherapy trials in cancer patients.
采用固相放射免疫分析法测定了48名正常供体和60名膀胱癌患者血清中针对卡介苗（BCG）的抗体水平。在57名参与BCG免疫疗法随机前瞻性对照试验的患者中，47名患者接受了长达30个月的随访，从而能够比较临床过程中特定时间点的肿瘤复发情况、对纯化蛋白衍生物（PPD）的迟发性皮肤超敏反应以及血清BCG抗体水平。BCG治疗前，正常供体和癌症患者血清中的BCG抗体水平同样较低。膀胱内和经皮给予BCG后，24名接受随机BCG免疫疗法的患者中有23名血清BCG抗体水平显著升高。在24名接受BCG治疗的患者中，14名患者的PPD皮肤试验反应和血清BCG抗体水平作为免疫反应指标密切相关，而在另外10名患者中，血清BCG抗体水平升高是比PPD皮肤试验反应更好的反应指标。随机分为非BCG治疗组的23名患者中有11名出现肿瘤复发，而BCG治疗组的24名随机患者中只有6名出现肿瘤复发。另外两名未随机分组但接受BCG治疗的患者出现肿瘤复发。所有8名出现肿瘤复发的接受BCG治疗的患者在BCG治疗后血清BCG抗体水平均有记录的升高。这8名患者中只有3名的PPD皮肤试验反应从阴性转为阳性；3名在免疫治疗前为阳性，2名在BCG治疗后仍为阴性。在正常供体以及BCG和非BCG治疗组的随机膀胱癌患者血清中，与5型人腺病毒和大肠杆菌抗原反应的抗体水平相似。这些结果表明，在癌症患者的免疫治疗试验中，血清BCG抗体反应在识别对免疫佐剂BCG的免疫反应方面与PPD皮肤试验同样有用。
