HER1-and HER2-targeted drugs are effective in cancer therapy, especially against lung, breast and colon malignancies; however, resistance of cancer cells to HER1-and HER2-targeted therapies is becoming a serious problem. The avidity/affinity constant (K_A) and growth inhibitory effect of anti-HER3 rat monoclonal antibodies (mAb, Ab1∼Ab6) in the presence of therapeutic mAb or low-molecular-weight inhibitors against HER family proteins were analyzed by flow cytometry-based Scatchard plots (Splot) and cell proliferation assay. The K_A of Ab3 and Ab6, but not Ab1 or Ab4, split into dual (high and low) modes of K_A, and Ab6 exhibited greater anti-proliferative effects against LS-174T colon cancer cells in the presence of Pertuzumab (anti-HER2 mAb). A high K_A by Ab6 and Ab6-mediated increased growth inhibition were observed against NCI–H1838 lung or BT474 breast cancer cells, respectively, in the presence of Panitumumab (anti-HER1 mAb) or Perutuzumab. A high K_A by Ab6 and Ab6-mediated increased anti-proliferative effects against NCI–H1838 or BT474 were also respectively observed in the presence of Erlotinib (HER1 inhibitor) or Lapatinib (HER1/HER2 inhibitor). In HER1-knockout (KO) NCI–H1838, the reactivity and K_A of Ab4 increased compared with in parent NCI–H1838. In HER1-KO or HER3-KO SW1116 colon cancer cells, dual modes of K_A with Pertuzumab were noted, and the combination Ab6 and Pertuzumab promoted growth inhibition of HER1-KO, but not of parent SW1116.

HER1 和 HER2 靶向药物在癌症治疗中有效，尤其是针对肺癌、乳腺癌和结肠恶性肿瘤；然而，癌细胞对 HER1 和 HER2 靶向疗法的耐药性正在成为一个严重的问题。在治疗性 mAb 或针对 HER 家族蛋白的低分子量抑制剂存在下，抗 HER3 大鼠单克隆抗体 (mAb、Ab1∼Ab6)的亲和力/亲和力常数 (K _A ) 和生长抑制作用通过流式细胞术分析-基于 Scatchard 图 (Splot) 和细胞增殖测定。Ab3 和 Ab6的 K _A，但不是 Ab1 或 Ab4，分裂为双重（高和低）K _A模式，并且 Ab6 在帕妥珠单抗（抗HER2 单克隆抗体）。高 K在存在帕尼单抗（抗 HER1 mAb）或佩妥珠单抗的情况下，分别观察到由 Ab6 和 Ab6 介导的_A对 NCI-H1838 肺癌或 BT474 乳腺癌细胞的生长抑制增加。高k_阿通过AB6和针对NCI-H1838或BT474 AB6介导的增加的抗增殖作用也分别在厄洛替尼（HER1抑制剂）或拉帕替尼（HER1 / HER2抑制剂）的存在下观察到。在HER1敲除（KO）NCI-H1838，反应性和K_甲Ab4的增加与在母体NCI-H1838进行比较。在HER1-KO或HER3-KO SW1116结肠癌细胞，K的双模式_阿与帕妥珠单抗，注意到，并且该组合AB6和帕妥珠单抗促进HER1-KO的生长抑制，但不是父SW1116。