Augmenting the immunogenicity of synthetic MUC1 peptide vaccines in mice.
Augmenting the immunogenicity of synthetic MUC1 peptide vaccines in mice.
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DOI：
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发表时间：
1996-07
期刊：
影响因子：
11.2
通讯作者：
S. Zhang;L. Graeber;F. Helling;G. Ragupathi;S. Adluri;K. Lloyd;P. Livingston
中科院分区：
文献类型：
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作者：
S. Zhang;L. Graeber;F. Helling;G. Ragupathi;S. Adluri;K. Lloyd;P. Livingston
人粘蛋白MUC1在某些上皮源性肿瘤中大量表达，在正常组织中主要局限于分泌细胞的顶面。因此，它是癌症免疫治疗的潜在靶点。在为临床试验做准备的过程中，将合成的不同长度和序列的MUC1多肽与不同佐剂混合或以不同的连接物方法共价连接到蛋白载体锁孔斑血蓝蛋白(KLH)上，在小鼠身上进行了研究。MUC1肽(含30个氨基酸)和佐剂QS-21或卡介苗不能诱导抗体产生。而与KLH结合的MUC1肽(MUClKLH)，加上QS-21，可诱导出针对免疫多肽和表达MUC1的肿瘤细胞的高滴度抗体。虽然在这些疫苗免疫的小鼠中没有观察到包括迟发型超敏反应、淋巴细胞增殖和CTL在内的T细胞反应，但在MUC1-KLH免疫的小鼠中观察到了对MUC1表达的肿瘤细胞的显著保护作用。在此基础上，构建了一种含有间马来酰亚胺基-N-羟基琥珀酰亚胺酯连接物和QS-21的MUC1-KLH结合物疫苗，用于临床试验。
Human mucin MUC1 is abundantly expressed in some cancers of epithelia] origin and is largely restricted to the apical surface of secretory cells in normal tissues. It is, therefore, a potential target for cancer immunotherapy. In preparation for clinical trials, vaccines containing synthetic MUC1 peptides of different lengths and sequences mixed with various adjuvants or covalently attached, using different linker methods, to protein carrier keyhole limpet hemocyanin (KLH) were studied in mice. MUC1 peptides (containing 30 amino acids), plus adjuvants QS-21 or Bacillus Calmette-Guerin, were incapable of inducing antibody. However, MUC1 peptides conjugated to KLH (MUCl-KLH), plus QS-21, induced high titer antibody against the immunizing peptides and against MUC1-expressing tumor cells. Although T-cell responses, including delayed-type hypersensitivity, lymphocyte proliferation, and CTL, were not observed in mice immunized with these vaccines, significant protection from MUC1-expressing tumor cell challenge in mice immunized with MUC1-KLH was observed. Based on these studies, a vaccine containing MUC1-KLH conjugate prepared with m-maleimidobenzoyl-N-hydroxysuccinimide ester linker, plus QS-21, has been constructed for testing in clinical trials.