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在接种基因修饰的同种异体肿瘤细胞的乳腺癌患者中鉴定肿瘤特异性抗体。

Identification of tumor-specific antibodies in patients with breast cancer vaccinated with gene-modified allogeneic tumor cells.

作者信息

Dols Annemieke, Meijer Sybren L, Hu Hong-Ming, Goodell Vivian, Disis Mary L, Von Mensdorff-Pouilly Silvia, Verheijen Rene, Alvord W Gregory, Smith John W, Urba Walter J, Fox Bernard A

机构信息

Robert W. Franz Cancer Research Center, Earle A Chiles Research Institute, Providence Portland Medical Center, Portland, Oregon, USA.

出版信息

J Immunother. 2003 Mar-Apr;26(2):163-70. doi: 10.1097/00002371-200303000-00009.

Abstract

Thirty HLA-A2 women with metastatic breast cancer received up to 14 vaccinations with MDA-MB-231-CD80, an HLA-A2 allogeneic breast cancer cell line, which had been lipofected with the cDNA for the CD80 costimulatory molecule. Tumor cells were administered with BCG or GM-CSF as an adjuvant. Sera obtained before and after vaccination were analyzed for antibodies to tumor cell lysate, MUC1, HER2/neu and p53. Since the cell line was grown in fetal bovine serum (FBS), sera were also analyzed for antibodies to FBS. Eighteen of 24 patients for whom sera were available exhibited anti-FBS activity at baseline. Eleven of these 18 patients and all six patients without baseline anti-FBS activity showed an increased titer after vaccination. The anti-FBS activity required that serum samples be absorbed in excess FBS to detect specific antibodies to tumor cell lysate. A two-fold increase in the titer of IgG specific to tumor cell lysate was observed in 6 patients. Eight of 24 patients made an antibody response to HER-2/neu, four of 24 to MUC1 and one of 24 to p53. Although antibody production to a variety of tumor cell-associated antigens was detected our results suggest that a whole cell vaccine comprising a CD80-transfected allogeneic breast cancer cell line with adjuvant BCG or GM-CSF was not a reliable method to induce significant antibody responses in women with advanced breast cancer.

摘要

30名HLA - A2型转移性乳腺癌女性患者接受了多达14次用MDA - MB - 231 - CD80(一种HLA - A2同种异体乳腺癌细胞系,已用CD80共刺激分子的cDNA进行脂质转染)进行的疫苗接种。肿瘤细胞与卡介苗(BCG)或粒细胞巨噬细胞集落刺激因子(GM - CSF)作为佐剂一起给药。对接种前后获得的血清进行分析,检测针对肿瘤细胞裂解物、黏蛋白1(MUC1)、人表皮生长因子受体2/neu(HER2/neu)和p53的抗体。由于该细胞系在胎牛血清(FBS)中培养,因此也对血清进行了针对FBS抗体的分析。在有血清样本的24名患者中,18名在基线时表现出抗FBS活性。这18名患者中的11名以及所有6名无基线抗FBS活性的患者在接种后滴度升高。抗FBS活性要求血清样本用过量FBS吸收以检测针对肿瘤细胞裂解物的特异性抗体。在6名患者中观察到针对肿瘤细胞裂解物的IgG滴度增加了两倍。24名患者中有8名对HER - 2/neu产生抗体反应,24名中有4名对MUC1产生抗体反应,24名中有1名对p53产生抗体反应。尽管检测到针对多种肿瘤细胞相关抗原的抗体产生,但我们的结果表明,包含用CD80转染的同种异体乳腺癌细胞系与佐剂BCG或GM - CSF的全细胞疫苗并不是在晚期乳腺癌女性中诱导显著抗体反应的可靠方法。

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