chFRP5-ZZ-PE38, a large IgG-toxin immunoconjugate outperforms the corresponding smaller FRP5(Fv)-ETA immunotoxin in eradicating ErbB2-expressing tumor xenografts.
chFRP5-ZZ-PE38, a large IgG-toxin immunoconjugate outperforms the corresponding smaller FRP5(Fv)-ETA immunotoxin in eradicating ErbB2-expressing tumor xenografts.
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chFRP5-ZZ-PE38 是一种大型 IgG 毒素免疫缀合物，在根除表达 ErbB2 的肿瘤异种移植物方面优于相应的较小 FRP5(Fv)-ETA 免疫毒素。
DOI：
10.1016/j.canlet.2007.07.009
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发表时间：
2007
期刊：
影响因子：
9.7
通讯作者：
I. Benhar
中科院分区：
文献类型：
--
作者：
Yariv Mazor;R. Noy;W. Wels;I. Benhar
作为治疗方法，抗体可以“非武装”使用，也可以作为免疫偶联物使用，将细胞毒性部分引导至肿瘤细胞。免疫缀合物是通过将化疗药物、放射性同位素或毒素附着到抗体上而制成的。与细胞毒性部分融合的小型重组抗体片段（称为重组免疫毒素）也正在开发中，作为靶向癌症治疗的另一种方法。确定此类靶向治疗的治疗潜力的关键参数是靶点特异性、亲和力、稳定性和大小。在治疗实体瘤方面，肿瘤渗透（与大小成反比）目前被认为是疗效的主要因素，而结合亲和力和在体内的停留时间等参数被认为贡献较小。当比较重组免疫毒素和针对 ErbB2/HER2 的抗体-毒素免疫偶联物时，我们发现二价抗体-毒素免疫偶联物 (200kDa) 在杀死培养物和裸鼠异种移植物中表达 ErbB2 的肿瘤细胞方面优于相应的重组单价免疫毒素 (69kDa)，这表明更高的亲和力和更长的停留时间可能超过肿瘤渗透。我们的研究表明，重新评估目前被忽视的大型 IgG 效应分子缀合物用于抗癌治疗可能是合理的。
As therapeutics, antibodies can be used “un-armed” or as immunoconjugates to direct cytotoxic moieties to tumor cells. Immunoconjugates are made by attaching chemotherapy drugs, radioisotopes or toxins to the antibody. Small recombinant antibody fragments fused to cytotoxic moieties, termed recombinant immunotoxins are also being developed as an additional approach for a targeted cancer therapy. Key parameters in determining the therapeutic potential of such targeted therapies are target specificity, affinity, stability and size. With regard to treating solid tumors, tumor penetration (which is inversely proportional to size) is currently regarded as the prime factor for efficacy, while parameters such as binding affinity and residence time in the body are thought to contribute to a lesser extent. When comparing recombinant immunotoxins and antibody-toxin immunoconjugates that target ErbB2/HER2, here we found that a bivalent antibody-toxin immunoconjugate (200kDa) was superior to the corresponding recombinant monovalent immunotoxin (69kDa) in killing ErbB2-expressing tumor cells in culture and as xenografts in nude mice, suggesting that higher avidity and longer residence time may outweigh tumor penetration. Our study suggests that the re-valuation of currently neglected, large IgG-effector molecule conjugates for anti-cancer therapy may be justified.
影响因子：
3.4
作者：
Posey, JA;Khazaeli, MB;LoBuglio, AF
通讯作者：
LoBuglio, AF
影响因子：
4.7
作者：
Schmidt, M;McWatters, A;Bast, RC
通讯作者：
Bast, RC