Patterson James T, Gros Edwige, Zhou Heyue, Atassi Ghazi, Kerwin Lisa, Carmody Lisa, Zhu Tong, Jones Bryan, Fu Yanwen, Kaufmann Gunnar F
Sorrento Therapeutics, Inc., 4955 Directors Place, San Diego, CA 92121, USA.
Sorrento Therapeutics, Inc., 4955 Directors Place, San Diego, CA 92121, USA.
Bioorg Med Chem Lett. 2017 Aug 15;27(16):3647-3652. doi: 10.1016/j.bmcl.2017.07.021. Epub 2017 Jul 8.
Bispecific antibodies (BsAbs) are designed to engage two antigens simultaneously, thus, effectively expanding the ability of antibody-based therapeutics to target multiple pathways within the same cell, engage two separate soluble antigens, bind the same antigen with distinct paratopes, or crosslink two different cell types. Many recombinant BsAb formats have emerged, however, expression and purification of such constructs can often be challenging. To this end, we have developed a chemical strategy for generating BsAbs using native IgG2 architecture. Full-length antibodies can be conjugated via disulfide bridging with linkers bearing orthogonal groups to produce BsAbs. We report that an αHER2/EGFR BsAb was successfully generated by this approach and retained the ability to bind both antigens with no significant loss of potency.
双特异性抗体（BsAbs）旨在同时结合两种抗原，因此能有效扩展基于抗体的治疗药物靶向同一细胞内多种途径、结合两种不同可溶性抗原、以不同抗原结合位点结合相同抗原或交联两种不同细胞类型的能力。许多重组双特异性抗体形式已经出现，然而，此类构建体的表达和纯化往往具有挑战性。为此，我们开发了一种利用天然IgG2结构生成双特异性抗体的化学策略。全长抗体可通过二硫键桥接与带有正交基团的连接子缀合以产生双特异性抗体。我们报道通过这种方法成功生成了一种αHER2/EGFR双特异性抗体，并且该抗体保留了结合两种抗原的能力，效力没有显著损失。
