Pan-HER, an Antibody Mixture Simultaneously Targeting EGFR, HER2, and HER3, Effectively Overcomes Tumor Heterogeneity and Plasticity

摘要: Purpose: Accumulating evidence indicates a high degree of plasticity and compensatory signaling within the human epidermal growth factor receptor (HER) family, leading to resistance upon therapeutic intervention with HER family members. Experimental Design/Results: We have generated Pan-HER, mixture six antibodies targeting each members EGFR, HER2, HER3 synergistic pairs antibodies, which simultaneously remove all three targets, thereby preventing tumor promoting mechanisms family. Pan-HER induces potent inhibition in range cancer cell lines xenograft models, including acquired antibodies. is also highly efficacious presence ligands, indicating that it capable overcoming due increased ligand production. All target specificities contribute enhanced efficacy, demonstrating distinct benefit combined when compared single-receptor targeting. Conclusions: Our data show simultaneous receptors provides broader efficacy than single or any combination two especially ligands. represents novel strategy deal primary heterogeneity terms dependency as such may be viable alternative clinic. Clin Cancer Res; 21(18); 4110–22. ©2015 AACR . See related commentary by Yarden Sela, [p. 4030][1] This article featured Highlights This Issue, 4025][2] [1]: /lookup/volpage/21/4030?iss=18 [2]: /lookup/volpage/21/4025?iss=18