ADC Development Services Targeting HER3

As a new and promising therapeutic method, antibody-drug conjugates (ADCs) combine the target specificity of an antibody with the high potency of a synthetic small molecule. It is critical to construct a successful ADC through optimal conjugation strategies.

Creative Biolabs has rich experience in providing custom bio-conjugation service for the biomedical research community, biotechnology and pharmaceutical companies, and has consistently met the highest ADCs standards of quality. With over ten years of practical antibody production and drug synthesis experience, we have developed highly specific expertise to develop ADCs. With a diverse range of modifications available for linkers or linker-payloads, we are able to meet our clients' specific requirments.

Introduction of HER3+

Human epidermal growth receptors (EGFR/HER) family contains four members including the EGFR/ERBB1/HER1, ERBB2/HER2/Neu, ERBB3/HER3 and ERBB4/HER4. They are highly expressed in numerous cells, such as epithelial, neuronal, tumor and mesenchymal cells and involved in cell division, cell proliferation, differentiation, angiogenesis and tumor progression. HER3 is encoded by the HER3 gene located at the long arm of chromosome 12 (12q13). It consists of an extracellular domain (ECD), a transmembrane domain, an intracellular domain with tyrosine kinase (TK) activity and a C-terminal tail. HER3 is widely expressed on various solid tumors, such as the ovarian, breast, prostate, gastric, bladder, lung, melanoma, colorectal and squamous cell carcinoma. Besides, it acts as the heterodimeric partner of EGFR exists in melanoma and pancreatic carcinoma. HER3 often shows a co-expression with HER2 in breast cancer and plays an important role in HER2-mediated tumorigenesis. Thus, HER3 is becoming a useful target in targeted immunotherapy for solid tumors.

HER3 binding partners and anti-HER3 targeted therapies in preclinical and clinical trials. Fig.1 HER3 binding partners and anti-HER3 targeted therapies in preclinical and clinical trials. (Rosalin, 2018)

Anti-HER3 ADC in Solid Tumors

HER3 is overexpressed in a variety of solid tumors and is used in ADCs design for the cancer therapy. For example, U3-1402 is a HER3-targeted antibody-drug conjugate. The ADC is composed of an anti-HER3 monoclonal antibody (patritumab) linked to the topoisomerase I inhibitor DX 8951 via a cleavable GGFG peptide linker. DX 8951 is a semisynthetic, water-soluble derivative of camptothecin with antineoplastic activity. Upon U3-1402 binding to the HER3, it can be internalized rapidly and release the potent payload to inhibit the replication of DNA and induce the tumor cell death.

During the preclinical studies, U3-1402 showed powerful cytotoxic activity in tumor cell lines, xenograft mouse models and patient-derived xenograft (PDX) models. In addition, clinical trials results in phase 1/2 demonstrated that U3-1402 has significant antitumor activity in a large number of heavily pretreated HER3-positive metastatic breast cancer (MBC) patients with a manageable safety profile. Therefore, this ADC may be a potential and effective therapeutic agent in the solid tumors treatments.

The structure and preclinical trials of U3-1402 ADC. Fig.2 The structure and preclinical trials of U3-1402 ADC. (Yonesaka, 2019)

What Can We Do for You?

Creative Biolabs provides one-stop-shop custom ADCs development services targeting different biomarkers such as the HER3, and our services include antibody and drug preparation, modification, conjugation, and purification. We also have the ability to characterize and test the conjugates. Hence, in a typical service, customers can provide antibody, payload, specify target for conjugation or just an idea, then we will design the optimal approach to generate the final product.

Please click below links to discover more about our custom ADCs services.

For more information, please feel free to contact us.

References

  1. Rosalin, M.; et al. Her3 signaling and targeted therapy in cancer. Oncology Reviews. 2018, 12(1).
  2. Yonesaka, K.; et al. An HER3-targeting antibody-drug conjugate incorporating a DNA topoisomerase I inhibitor U3-1402 conquers EGFR tyrosine kinase inhibitor-resistant NSCLC. Oncogene. 2019, 38(9): 1398.

For lab research use only, not for any in vivo human use.


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