BIOUNIVERSA s.r.l., R&D Division, University of Salerno, Baronissi, Italy.
Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, Italy.
Mol Oncol. 2019 Jun;13(6):1388-1399. doi: 10.1002/1878-0261.12492. Epub 2019 May 17.
We have previously shown that secreted BAG3 is a potential target for the treatment of pancreatic ductal adenocarcinoma and that pancreatic tumor growth and metastatic dissemination can be reduced by treatment with an anti-BAG3 murine antibody. Here, we used complementarity-determining region (CDR) grafting to generate a humanized version of the anti-BAG3 antibody that may be further developed for possible clinical use. We show that the humanized anti-BAG3 antibody, named BAG3-H2L4, abrogates BAG3 binding to macrophages and subsequent release of IL-6. Furthermore, it specifically localizes into tumor tissues and significantly inhibits the growth of Mia PaCa-2 pancreatic cancer cell xenografts. We propose BAG3-H2L4 antibody as a potential clinical candidate for BAG3-targeted therapy in pancreatic cancer.
我们之前已经表明，分泌型 BAG3 是治疗胰腺导管腺癌的一个潜在靶点，并且用抗 BAG3 鼠抗体进行治疗可以减少胰腺肿瘤的生长和转移扩散。在这里，我们使用互补决定区（CDR）移植来生成抗 BAG3 抗体的人源化版本，该抗体可能会进一步开发用于可能的临床用途。我们表明，这种称为 BAG3-H2L4 的人源化抗 BAG3 抗体可阻断 BAG3 与巨噬细胞的结合以及随后的 IL-6 释放。此外，它还特异性地定位于肿瘤组织中，并显著抑制 Mia PaCa-2 胰腺癌细胞异种移植物的生长。我们提出 BAG3-H2L4 抗体作为针对胰腺癌的 BAG3 靶向治疗的潜在临床候选药物。
