免疫促凋亡分子靶向杀伤肿瘤的研究进展

The Progress in Immunoproapoptotin Molecules Targeting Tumor Cells

免疫促凋亡分子是肿瘤特异性表面标记物的单链抗体与具有转位及杀伤功能的活性片段融合表达的重组蛋白，具有靶向识别、高效杀伤肿瘤细胞的特点。免疫促凋亡分子由免疫毒素发展而来，免疫毒素虽然具有较强的杀伤活性和特异性，但是由于其转运、杀伤结构域来源于细菌或植物毒素，临床试验中产生了中和抗体并伴有较强副作用，限制了其应用的范围。第二代免疫促凋亡分子利用人内源性杀伤分子替换了免疫毒素的杀伤结构域，部分解决了免疫毒素的免疫原性问题，但是其未被替代的天然毒素转位结构域仍具有免疫原性且转位效率有限。最新一代免疫促凋亡分子进一步用furin位点替代了毒素的转位结构域，在保证特异性及杀伤活性的同时，提高了转位能力并极大地降低了免疫原性，因而具有广泛的临床应用前景。

Immunoproapoptotin consists of a single-chain antibody against tumor-specific surface marker and an active domain which has the function of translocation and pm-apoptosis. This fused recombinant protein can specifically recognize and kill tumor cells. Immunoproapoptotin comes from immunotoxin which is proved not successful in clinical trials by inducing neutralizing antibody and other side effects due to the heterogenous toxins domains from bacteria or plants. To avoid the immunogenicity of immunotoxin, effectors from human were employed in the 2rid generation of Immunoproapoptotin. However, the translocation domain is still heterogenous and the efficiency of translocation is limited. In the latest progress, a furin cleavage site was used to substitute for the translocation domain and thus enhanced the translocation efficiency and greatly reduced the immunogenicity of Immunoproapoptotin, demonstrating a wide clinical application prospects.