Ad5/3能够通过与红细胞和淋巴细胞结合而避免中和
Ad5/3 is able to avoid neutralization by binding to erythrocytes and lymphocytes
原文发布日期:2020-09-12
英文摘要:
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原文链接:
Oncolytic adenoviruses are promising cancer therapeutic agents. Clinical data have shown adenoviruses’ ability to transduce tumors after systemic delivery in human cancer patients, despite antibodies. In the present work, we have focused on the interaction of a chimeric adenovirus Ad5/3 with human lymphocytes and human erythrocytes. Ad5/3 binding with human lymphocytes and erythrocytes was observed to occur in a reversible manner, which allowed viral transduction of tumors, and oncolytic potency of Ad5/3 in vitro and in vivo, with or without neutralizing antibodies. Immunodeficient mice bearing xenograft tumors showed enhanced tumor transduction following systemic administration, when Ad5/3 virus was bound to lymphocytes or erythrocytes (P < 0.05). In conclusion, our findings reveal that chimeric Ad5/3 adenovirus reaches non-injected tumors in the presence of neutralizing antibodies: it occurs through reversible binding to lymphocytes and erythrocytes.
溶瘤腺病毒是一类具有前景的癌症治疗制剂。临床数据显示,尽管存在抗体,腺病毒在全身给药后仍能转导人类癌症患者的肿瘤。本研究重点关注嵌合腺病毒Ad5/3与人类淋巴细胞及红细胞的相互作用。观察到Ad5/3与人类淋巴细胞和红细胞的结合以可逆方式发生,这种特性使得病毒在存在或不存在中和抗体的情况下均能实现肿瘤转导,并在体外和体内展现溶瘤效力。在携带异种移植瘤的免疫缺陷小鼠中,当Ad5/3病毒与淋巴细胞或红细胞结合后经全身给药,可显著增强肿瘤转导效率(P<0.05)。综上所述,我们的研究结果表明:嵌合Ad5/3腺病毒通过可逆性结合淋巴细胞和红细胞,能在中和抗体存在的情况下抵达非注射部位的肿瘤。
Ad5/3 is able to avoid neutralization by binding to erythrocytes and lymphocytes
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