抗体
子类
化学
单克隆抗体
分子生物学
体内分布
医学
免疫球蛋白G
新生儿Fc受体
体内
同型
作者
Sai Kiran Sharma,Maya Suzuki,Hong Xu,Joshua A. Korsen,Zachary Samuels,Hong-fen Guo,Brandon Nemieboka,Alessandra Piersigilli,Kimberly J. Edwards,Nai-Kong V. Cheung,Jason S. Lewis
标识
DOI:10.2967/jnumed.121.262383
摘要
Immuno-positron emission tomography (immuno-PET) is a powerful tool to noninvasively characterize the in vivo biodistribution of engineered antibodies (Abs). Methods L1 cell adhesion molecule (L1CAM)-targeting HuE71 immunoglobulin G1 (IgG1) and immunoglobulin G4 (IgG4) Abs bearing identical variable heavy and light chain sequences but different fragment crystallizable (Fc) portions were radiolabeled with Zirconium-89 (89Zr) and the in vivo biodistribution was studied in SKOV3 ovarian cancer xenografted nude mice. Results In addition to showing uptake in L1CAM-expressing SKOV3 tumors like its parental counterpart HuE71 IgG1, the afucosylated variant having enhanced Fc-receptor (FcR) affinity showed high nonspecific uptake in lymph nodes. On the other hand, aglycosylated HuE71 IgG1 with abrogated FcR binding did not show lymphoid uptake. The use of IgG4 subclass showed high nonspecific uptake in the kidneys, which was prevented by mutating serine at position 228 to proline (S228P) in the hinge region of the IgG4 Ab to mitigate in vivo fragment antigen-binding (Fab) arm exchange. Conclusion Our findings highlight the influence of Fc-modifications and the choice of IgG subclass on the in vivo biodistribution of Abs and the potential outcomes thereof.
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