Genomics Research Center and Chemical Biology and Molecular Biophysics, Taiwan International Graduate Program, Academia Sinica, Taipei 115, Taiwan.
Proc Natl Acad Sci U S A. 2013 Feb 12;110(7):2517-22. doi: 10.1073/pnas.1222649110. Epub 2013 Jan 25.
Globo H (GH) is a hexasaccharide specifically overexpressed on a variety of cancer cells and therefore, a good candidate for cancer vaccine development. To identify the optimal carrier and adjuvant combination, we chemically synthesized and linked GH to a carrier protein, including keyhole limpet hemocyanion, diphtheria toxoid cross-reactive material (CRM) 197 (DT), tetanus toxoid, and BSA, and combined with an adjuvant, and it was administered to mice for the study of immune response. Glycan microarray analysis of the antiserum obtained indicated that the combination of GH-DT adjuvanted with the α-galactosylceramide C34 has the highest enhancement of anti-GH IgG. Compared with the phase III clinical trial vaccine, GH-keyhole limpet hemocyanion/QS21, the GH-DT/C34 vaccine elicited more IgG antibodies, which are more selective for GH and the GH-related epitopes, stage-specific embryonic antigen 3 (SSEA3) and SSEA4, all of which were specifically overexpressed on breast cancer cells and breast cancer stem cells with SSEA4 at the highest level (>90%). We, therefore, further developed SSEA4-DT/C34 as a vaccine candidate, and after immunization, it was found that the elicited antibodies are also IgG-dominant and very specific for SSEA4.
Globo H (GH) 是一种六糖，在多种癌细胞上特异性过表达，因此是癌症疫苗开发的良好候选物。为了确定最佳载体和佐剂组合，我们通过化学合成将 GH 连接到载体蛋白上，包括钥孔贻贝血蓝蛋白、白喉类毒素交叉反应物质 (CRM) 197 (DT)、破伤风类毒素和 BSA，并与佐剂结合，然后将其施用于小鼠以研究免疫反应。对获得的抗血清进行糖基微阵列分析表明，与佐剂 α-半乳糖基神经酰胺 C34 联合的 GH-DT 增强了抗 GH IgG 的效果最佳。与 III 期临床试验疫苗 GH-钥孔贻贝血蓝蛋白/QS21 相比，GH-DT/C34 疫苗诱导产生了更多的 IgG 抗体，这些抗体对 GH 及其相关表位、阶段特异性胚胎抗原 3 (SSEA3) 和 SSEA4 具有更高的选择性，所有这些表位均在乳腺癌细胞和乳腺癌干细胞上特异性过表达，其中 SSEA4 的表达水平最高（>90%）。因此，我们进一步开发了 SSEA4-DT/C34 作为疫苗候选物，免疫后发现诱导的抗体也以 IgG 为主，并且对 SSEA4 具有非常特异性。
