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目的:研究抗Pgp/抗CD3微型双功能抗体的体内作用。方法:125I标记抗Pgp/抗CD3微型双功能抗体采用氯胺T法,并采用昆明鼠和人K562耐药裸鼠移植瘤模型分别测定该微型双功能抗体在小鼠体内的药代动力学和体内组织分布;采用人K562耐药及敏感裸鼠移植瘤模型测定该微型双功能抗体介导的体内靶向杀伤活性及其不良反应。结果:抗Pgp/抗CD3微型双功能抗体在昆明鼠体内的半衰期为2h;尾静脉注射抗Pgp/抗CD3微型双功能抗体6h后,其在肿瘤部位的分布高于其他组织,在12h和24h时,其在肿瘤与血液分布的比率分别为2.69和8.09;抗Pgp/抗CD3微型双功能抗体能介导人T细胞有效杀伤表达Pgp抗原的K562耐药细胞。结论:抗Pgp/抗CD3微型双功能抗体能在裸鼠皮下人白血病细胞移植瘤部位富集,并能有效地抑制耐药白血病移植瘤的生长,无明显的不良反应。
AIM: To study the in vivo effects of anti-Pgp / anti-CD3 microbifunctional antibodies. Methods: 125I-labeled anti-Pgp / anti-CD3 micro-bifunctional antibody was determined by chloramine T method and the Kunming mouse and human K562-resistant nude mice xenograft model were used to determine the pharmacokinetics of the micro-bifunctional antibody Vivo distribution of the K562 drug-resistant and sensitive nude mice xenograft model was used to measure the in vivo anti-tumor activity and adverse reactions mediated by the bifunctional antibody. Results: The half-life of anti-Pgp / anti-CD3 antibody was 2 h in Kunming mice. The anti-Pgp / anti-CD3 antibody was higher than that of other tissues at 6 h , Respectively. The ratios of tumor to blood distribution were 2.69 and 8.09, respectively. Anti-Pgp / anti-CD3 micro-bifunctional mediators could mediate that human T cells effectively kill K562 resistant cells expressing Pgp antigen. CONCLUSION: The anti-Pgp / anti-CD3 micro-bifunctional antibody can be enriched in transplanted subcutaneous human leukemia cell xenografts in nude mice and can effectively inhibit the growth of transplanted tumor resistant leukemia without obvious adverse reactions.