ERBB2 Specific Neutra™ Antibody Products

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ERBB2, belonging to the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases, lacks its own ligand binding domain, rendering it incapable of directly binding to growth factors. However, it forms tight associations with other EGF receptor family-bound ligands, leading to the stabilized formation of heterodimers. Amplification and/or overexpression of ERBB2 have been observed in many kinds of cancers, including ovarian and breast tumors. Alternative splicing produces several additional transcript variants, some encoding different isoforms, while others remain incompletely characterized.

Its Gene ID: 2064, UniProtKB ID: P04626, and OMIM ID: 164870.

ERBB2 Related Signaling Pathways

Dysregulation of the PI3K/AKT/mTOR pathway is a prevalent occurrence in cancers, offering an attractive target for anticancer therapies. In ERBB2-positive breast cancer cells, ERBB2 directly engages with and is stabilized by DEPTOR. DEPTOR, characterized by a DEP domain and known as a mTOR-interacting protein, regulates mTOR activity, impacting cell proliferation and survival. The interaction between ERBB2 and DEPTOR transpires on the cell membrane, disrupting ERBB2 polyubiquitination and facilitating ERBB2 degradation, ultimately triggering apoptosis.

Fig. 1 A schematic diagram of DEPTOR-ERBB2 interplay regulating cell survival and proliferation in ERBB2-positive breast cancer cells. (Bi, et al., 2021) Fig.1 A schematic diagram of DEPTOR-ERBB2 interplay regulating cell survival and proliferation in ERBB2-positive breast cancer cells.¹

ERBB2 Stands Out as an Ideal Target for Antitumor Treatment

Amplification of the ERBB2 gene or overexpression of the ERBB2 receptor plays a significant role in cellular transformation, carcinogenesis, and the prognosis of various cancer types. ERBB2-targeted immunotherapy encompasses bispecific antibodies, activated T cells armed with anti-ERBB2 bispecific antibodies, and monoclonal antibodies. Conventional methods for assessing ERBB2 expression include fluorescence in situ hybridization (FISH) or immunohistochemistry staining (IHC) [Anti-ERBB2 Neutralizing Antibody (V3S-0622-YC1482)] at the primary site. Additionally, the detection of circulating tumor cells (CTCs) is considered a promising method.

Anti-ERBB2 monoclonal antibodies play an important role in breast cancer

ERBB2, also known as HER2, serves as a tumor-associated antigen that can be targeted through diverse treatment strategies. ERBB2-positive breast cancer constitutes a significant proportion of breast cancer cases. Monoclonal antibodies (mAbs) directed against ERBB2 have shown considerable clinical efficacy in a subset of patients with ERBB2-positive breast cancer. These mAbs directly target ERBB2, resulting in the downregulation of oncogenic intracellular pathways activated by ERBB2 through homo- and hetero-dimerization on the cancer cell membrane. Thus, the ERBB2-adaptive immune response is reinforced by both CD4⁺ and CD8⁺ T cells, which secrete Th1 cytokines.

Fig. 2 Visualizing the immune response to HER2-expressing breast cancer. (Costa, et al., 2020) Fig.2 Visualizing the immune response to HER2-expressing breast cancer.²

Anti-ERBB2 mAb in tumor suppression and immune response

The anti-ERBB2 mAb reduces ERBB2 expression by promoting receptor internalization and degradation. A published mAb, which binds to extracellular subdomain IV of ERBB2, impedes ERBB2 homodimerization, inhibiting downstream Ras/Raf/MAPK and PI3K/Akt pathways and exhibiting anti-angiogenic effects. The Fc fragment of the mAb, upon binding to NK cells, induces robust antibody-dependent cellular cytotoxicity assay (ADCC) and cytokine secretion for effective tumor cell elimination. Additionally, Creative Biolabs provides Recombinant Anti-ERBB2 (ECD domain) Antibody (V3S-0822-YC2967), Recombinant Anti-ERBB2 (ECD domain) Antibody (V3S-0822-YC2974) for detecting ERBB2 in ADCC assays.

Creative Biolabs offers a comprehensive selection of more than fifty anti-CD38 antibody products designed for research in therapies targeting breast cancer, gastro-esophageal junction cancers, gallbladder cancers, and other cancers. Additionally, we welcome inquiries for the customization of ERBB2-based bispecific antibodies.

REFERENCES

Bi, Yanli, et al. "DEPTOR stabilizes ErbB2 to promote the proliferation and survival of ErbB2-positive breast cancer cells." Theranostics 11.13 (2021): 6355.
Costa, Ricardo LB, and Brian J. Czerniecki. "Clinical development of immunotherapies for HER2+ breast cancer: a review of HER2-directed monoclonal antibodies and beyond." NPJ Breast Cancer 6.1 (2020): 10.

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