A Single Domain–Based Anti-Her2 Antibody Has Potent Antitumor Activities

Abstract

Human epidermal growth factor receptor 2 (HER2) is overexpressed in approximately 20% to 30% of breast cancers and various other types of cancers, which plays a vital role in the cancer progression. Monoclonal antibodies targeting Her2 are now used in the clinic to treat Her2 overexpression cancer patients. However, relapse or resistance is frequent with the current therapies. To generate a new treatment avenue against Her2, we immunized and selected a specific anti-Her2 single domain antibody C3 for further studies. The C3-Fc antibody drove antibody-dependent cell-mediated cytotoxicity against Her2-positive tumor cells in vitro and resulted in potent antitumor growth in vivo. These data suggest that the C3-Fc antibody may provide an alternative avenue for Her2-positive cancer therapy.

Expression and In Vitro Function of Anti-Breast Cancer Llama-Based Single Domain Antibody VHH Expressed in Tobacco Plants

“…From this point of view, the plant-derived anti-HER2 VHH-FcK antibody (anti-HER2 VHH-FcK P ) showed specific binding to HER2-positive tumor cells, consistent with the observation for Herceptin (positive control). The binding of anti-HER2 VHH-FcK to HER2 almost matched that of Herceptin, and anti-HER2 VHH-FcK showed higher affinity for tumor cell in vitro; this is suggestive of its potential as an alternative therapeutic approach for HER2-positive tumors [18].…”

“…In conclusion, a single llama-based anti-HER2 VHH-FcK was successfully expressed in tobacco, and it had specific binding activity to breast cancer cells expressing HER2 with inhibition activity on breast cancer cell migration. The efficient antitumor effects of the plant-derived anti-HER2 VHH-FcK-similar to those of the positive control Herceptin-may extend its application as an alternative approach to combat HER2-overexpressing tumors [18].…”

Bp-Bs, a Novel T-cell Engaging Bispecific Antibody with Biparatopic Her2 Binding, Has Potent Anti-tumor Activities

“…For example, only 15%–30% of Her2-positive patients respond to trastuzumab therapy due to de novo and acquired resistance 10, 11. Trastuzumab has minimal effects on Her2 low- or medium-expression cancer cells in vivo and in vitro 12, 13. Poor internalization also leads to resistance in T-DM1 treatment of metastatic breast cancer 10, 14, 15.…”

“…In previous studies, we have designed bispecific antibodies using anti-Her2 single-domain antibodies (or VH-only heavy-chain antibody [VHH]) that redirect immune cells toward Her2 cancer cells 13, 22, 23, 24. These bispecific antibodies exhibited potent cytotoxicity against Her2 medium- or high-expression cells 12, 22. However, these antibodies still had no or low cytotoxicity against Her2 low-expression cells, such as MCF7 cells 12, 22.…”

“…These bispecific antibodies exhibited potent cytotoxicity against Her2 medium- or high-expression cells 12, 22. However, these antibodies still had no or low cytotoxicity against Her2 low-expression cells, such as MCF7 cells 12, 22. As monovalent anti-Her2 was used in these formats, we reasoned that, by increasing the valency of the anti-Her2 module, the binding and cytotoxicity of the bispecific antibody may be enhanced.…”