Bispecific Antibody Molecule Inhibits Tumor Cell Proliferation More Efficiently Than the Two-Molecule Combination.

Background: Monoclonal antibodies (mAbs) have proved to be a valuable tool for the treatment of different cancer types. However, clinical use of an increasing number of mAbs, have also highlighted limitations with monotherapy for cancers, in particular for such with more complex mechanisms, requiring action on additional molecules or pathways, or for cancers quickly acquiring resistance following monotherapy. An example for the latter is the mAb trastuzumab, FDA approved for treatment of metastatic gastric carcinoma.

Establishment of a Patient-derived Xenograft for Development of Personalized HER2-targeting Therapy in Gastric Cancer.

Background/aim: To maximize success rate for development of HER2-targeted therapeutics, patient-derived xenograft (PDX) models reflecting HER2-positive gastric cancer (HER2 GC) patients were established.

Materials And Methods: GC tissues obtained from surgery of GC patients were implanted into immune-deficient mice, and tumor tissue of HER2 PDXs were verified of the patient-mimic HER2 expression by immunohistochemistry and explored for the feasibility by testing with Herceptin, the approved therapeutics and novel HER2 antibody therapeutics being developed.

Results: We obtained 5 cases of HER2 GC PDX models reflecting patient's GC tumor, consisting of 2 cases of HER2 3+ and 2 cases of HER2 2+.

Affinity Maturation of Monoclonal Antibody 1E11 by Targeted Randomization in CDR3 Regions Optimizes Therapeutic Antibody Targeting of HER2-Positive Gastric Cancer.

Anti-HER2 murine monoclonal antibody 1E11 has strong and synergistic anti-tumor activity in HER2-overexpressing gastric cancer cells when used in combination with trastuzumab. We presently optimized this antibody for human therapeutics. First, the complementarity determining regions (CDRs) of the murine antibody were grafted onto human germline immunoglobulin variable genes.

Combination of novel HER2-targeting antibody 1E11 with trastuzumab shows synergistic antitumor activity in HER2-positive gastric cancer.

The synergistic interaction of two antibodies targeting the same protein could be developed as an effective anti-cancer therapy. Human epidermal growth factor receptor 2 (HER2) is overexpressed in 20-25% of breast and gastric cancer patients, and HER2-targeted antibody therapy using trastuzumab is effective in many of these patients. Nonetheless, improving therapeutic efficacy and patient survival is important, particularly in patients with HER2-positive gastric cancer.