Immunization of high-risk breast cancer patients with clustered sTn-KLH conjugate plus the immunologic adjuvant QS-21
Immunization of high-risk breast cancer patients with clustered sTn-KLH conjugate plus the immunologic adjuvant QS-21
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DOI：
10.1158/1078-0432.ccr-06-2189
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发表时间：
2007-05-15
影响因子：
11.5
通讯作者：
Livingston, Philip O.
中科院分区：
文献类型：
--
作者：
Gilewski, Teresa A.;Ragupathi, Govind;Livingston, Philip O.
目的：观察聚集性sTn-KLH [sTn (c) -KLH]偶联物加QS-21免疫高危乳腺癌患者后对sTn和表达sTn的肿瘤细胞的临床毒性和抗体反应。实验设计：27例无疾病证据、有IV期无疾病证据、肿瘤标志物上升、II期（>= 4个阳性腋窝淋巴结）或III期疾病病史的患者，在第1、2、3、7和19周共接受5次注射。免疫由sTn (c) - KLH结合物组成，含有30、10、3或1 μ g sTn (c)加100 μ g QS-21。在治疗前后，检测了抗合成sTn(c)和天然sTn的IgM和IgG抗体在羊颌下黏液蛋白上的诱导作用。荧光活化细胞分选分析评估抗体对LSC和MCF-7肿瘤细胞的反应性。结果：最常见的毒性是注射部位短暂的局部皮肤反应和轻微的流感样症状。所有患者均出现显著的抗sTn IgM和IgG抗体滴度(c)。针对羊颌下黏液蛋白的抗体滴度通常较低。21例患者观察到IgM与LSC肿瘤细胞的反应性，13例患者观察到MCF-7细胞的反应性。IgG对LSC细胞的反应性极低。结论：sTn (c) -KLH偶联物联合QS-21免疫对高危乳腺癌患者具有良好的耐受性和免疫原性。未来的试验将把sTn (c)作为一种多抗原疫苗的组成部分。
Purpose: To determine the clinical toxicities and antibody response against sTn and tumor cells expressing sTn following immunization of high-risk breast cancer patients with clustered sTn-KLH [sTn (c) -KLH] conjugate plus QS-21.Experimental Design: Twenty-seven patients with no evidence of disease and with a history of either stage IV no evidence of disease, rising tumor markers, stage II (>= 4 positive axillary nodes), or stage III disease received a total of five injections each during weeks 1, 2, 3, 7, and 19. Immunizations consisted of sTn (c) - KLH conjugate containing 30, 10, 3, or 1 mu g sTn (c) plus 100 mu g QS-21. Induction of IgM and IgG antibodies against synthetic sTn(c) and natural sTn on ovine submaxillary mucin were measured before and after therapy. Fluorescence-activated cell sorting analyses assessed reactivity of antibodies to LSC and MCF-7 tumor cells.Results: The most common toxicities were transient local skin reactions at the injection site and mild flu-like symptoms. All patients developed significant IgM and IgG antibody titers against sTn (c). Antibody titers against ovine submaxillary mucin were usually of lower titers. IgM reactivity with LSC tumor cells was observed in 21 patients and with MCF-7 cells in 13 patients. There was minimal IgG reactivity with LSC cells.Conclusion: Immunization with sTn (c) -KLH conjugate plus QS-21 is well tolerated and immunogenic in high-risk breast cancer patients. Future trials will incorporate sTn (c) as a component of a multiple antigen vaccine.