HER3: Emerging as a Key Epidermal Growth Factor Receptor (EGFR) in cancer immunotherapy

HER3 (also known as ERBB3) is a crucial member of the Epidermal Growth Factor Receptor (EGFR) family. It plays a significant role in cellular proliferation, survival, and differentiation via the PI3K/Akt, MAPK, and JAK/STAT signaling pathways. Even though HER3 signaling is essential for tissue growth and homeostasis, dysregulation of this signaling pathway is linked to the advancement of cancer, making it a potentially effective therapeutic target for several cancers.

Research into the function of HER3 in cancer has helped develop targeted treatments, such as monoclonal antibodies, small molecule inhibitors, and combination therapies.

Notably, developments in HER3-targeted antibody-drug conjugates (ADCs) hold promise, especially in the treatment of metastatic breast cancer and non-small cell lung cancer (NSCLC). One such ADC is Patritumab Deruxtecan. Promising clinical activity is also seen when bispecific antibodies, like zenocutuzumab, target HER3 and HER2.

Pharmaceutical companies actively pursue research and drug development efforts related to HER3 targeting. Sino Biological provides an extensive selection of recombinant HER3 proteins and antibodies to support research on HER3 signaling and evaluation of therapeutic efficacy.

Physiological and pathological roles

One important member of the EGFR family is HER3. It is recognized for controlling the activation of the PI3K/Akt, MAPK, and JAK/STAT signaling pathways (Figure 1), which controls cellular proliferation, survival, and differentiation.

Under typical physiological circumstances, HER3 plays a role in tissue growth and homeostasis. On the other hand, dysregulation of HER3 signaling has been linked to several cancers, including those of the breast, ovaries, prostate, and stomach. The distinctive characteristic of HER3 is its strong ability to form heterodimers with other members of the ERBB family, especially HER2, which can result in increased oncogenic signaling and resistance to treatment.

HER3 signaling boosts NSCLC cell growth and survival by forming heterodimers with EGFR, HER2, MET, AXL, or IGF-1R, activating multiple pathways.

Figure 1. HER3 signaling boosts NSCLC cell growth and survival by forming heterodimers with EGFR, HER2, MET, AXL, or IGF-1R, activating multiple pathways. Image Credit: Sino Biological Inc.

Bench to bedside

Research into the role of HER3 in tumor growth and resistance has prompted the development of HER3-targeted therapies for various cancers, including head and neck, stomach, lung, and breast cancers. Monoclonal antibodies, small molecule inhibitors, and combination therapies that target HER3 are being investigated in clinical trials. Progress in using ADCs to deliver cytotoxic payloads directed by HER3, such as patritumab deruxtecan (U3-1402), appears promising for treating breast and non-small cell lung cancer.

Being the first HER3 ADC submitted for marketing, the FDA's approval of U3-1402 for priority review in treating EGFRm NSCLC represents a significant achievement. In HER2-positive solid tumors, dual targeting of HER3 and HER2 with bi-specific antibodies, such as zenocutuzumab (MCLA-128), also exhibits clinical activity. Pharmaceutical firms are actively working to improve pipelines and launch successful drugs by conducting HER3-targeting research.

Table 1. Current Clinical Status Targeting HER3. Source: https://www.pharnexcloud.com/

Company Highest Clinical Status Conditions
Boehringer Ingelheim Approved Adenocarcinoma, Brain Tumor
Daiichi Sankyo Apply for Market Adenocarcinoma, Breast Tumor
Merck & Co. Apply for Market Adenocarcinoma, Breast Tumor
Bristol Myers Squibb Phase III Cholangiocarcinoma, Colon Cancer
Biokin Pharmaceutical Phase III Cholangiocarcinoma, Colon Cancer
Hummingbird Bioscience Pte Ltd Phase II Adenocarcinoma, Prostate Cancer
Merus NV Phase II Endometrial Cancer, Prostate Cancer
Xuanzhu Biopharmaceutical Co., Ltd. Phase II Lung Cancer
Caris Life Sciences inc Phase II Adenocarcinoma, Prostate Cancer

 

Therapies against HER3 under clinical development. Monoclonals antibodies (mAbs), bispecific antibodies (bAbs), antibody–drug conjugate (ADC) and other therapies such as HER3 vaccine

Figure 2. Therapies against HER3 under clinical development. Monoclonals antibodies (mAbs), bispecific antibodies (bAbs), antibody-drug conjugate (ADC), and other therapies, such as the HER3 vaccine. Image Credit: Sino Biological Inc.

Application in research

Recombinant HER3 proteins from Sino Biological are widely cited in reputable journals, indicating their critical role in HER3-related research. Using an SPR assay, Anna O. et al. examined the binding affinity between mono- or bi-valent anti-HER3 antibody and recombinant HER3 protein using human HER3 (Cat#: 10201-H08H, Sino Biological) and murine mErbB3 protein (Cat#: 51003-M08H, Sino Biological).

In a separate investigation, John L. and Anna O. et al. used an SPR assay to measure the binding affinity between HER3 and affibody molecules labeled with macrocyclic chelators NOTA using the hHER3-His protein (Cat#: 10201-H08H, Sino Biological) and hHER3-mFc protein (Cat#: 10201-H05H, Sino Biological).

Biophysical characteristics. The theoretical molecular weight (Mw), melting temperature (Tm), and KD values were measured with HER3 (Cat#: 10201-H08H, Sino Biological), mErbB3 (Cat#: 51003-M08H, Sino Biological), human serum albumin (HSA) and mouse serum albumin (MSA) in an SPR assay. Source: Sino Biological Inc.

Biophysical characteristics

The experimental molecular masses, affinities, and melting temperatures of the conjugates. The theoretical molecular mass is in parenthesis. His-HER3 (Cat#: 10201-H08H, Sino Biological) immobilized surface with 1500 RU (resonance units). mFc-HER3 (Cat#: 10201-H05H, Sino Biological) immobilized surface with 2500 RU. Source: Sino Biological Inc.

The experimental molecular masses, affinities, and melting temperatures of the conjugates

Representative sensorgrams. ABDErbB3-3 and ABDErbB3-27 binding to hErbB3 (Sino Biological) and human serum albumin (HSA)

Representative sensorgrams. ABDErbB3-3 and ABDErbB3-27 binding to hErbB3 (Sino Biological) and human serum albumin (HSA). Image Credit: Sino Biological Inc.

Featured recombinant HER3 proteins

  • Coverage of multiple species
  • HPLC-verified           
  • Activity-validated
  • Highly cited in reputable journals

Human HER3 protein (His tag)

HPLC-verified (Cat#: 10201-H08H)

Functional ELISA: Immobilized human NRG1-beta 1 (Cat#: 11609-H01H2) protein can bind human HER3 protein.

Functional ELISA: Immobilized human NRG1-beta 1 (Cat#: 11609-H01H2) protein can bind human HER3 protein. Image Credit: Sino Biological Inc.

Rat HER3 protein (His tag)

(Cat#: 80111-R08H)

Functional ELISA: Immobilized human NRG1 Beta 1 Fc (Cat#: 11609-H01H2) can bind rat HER3/ERBB3 protein.

Functional ELISA: Immobilized human NRG1 Beta 1 Fc (Cat#: 11609-H01H2) can bind rat HER3/ERBB3 protein. Image Credit: Sino Biological Inc.

Human HER3 protein (His & AVI tag)

HPLC-verified (Cat#: 10201-H49H-B)

Functional ELISA: Immobilized human NRG1-beta 1 can bind human HER3 protein

Functional ELISA: Immobilized human NRG1-beta 1 can bind human HER3 protein. Image Credit: Sino Biological Inc.

More recombinant HER3 proteins

Source: Sino Biological Inc.

Cat# Species Tag Expression Host Purity
10201-H02H Human hFc Tag HEK293 Cells ≥95% (SEC-HPLC)
10201-H08H Human His Tag HEK293 Cells ≥95% (SEC-HPLC)
10201-H49H-B Human His & AVI Tag HEK293 Cells >95% (SEC-HPLC)
51003-M02H Mouse hFc Tag HEK293 Cells ≥90% (SEC-HPLC)
51003-M08H Mouse His Tag HEK293 Cells ≥90% (SEC-HPLC)
51003-M49H-B Mouse His & AVI Tag HEK293 Cells ≥95% (SEC-HPLC)
90043-K08H Rhesus His Tag HEK293 Cells ≥95% (SEC-HPLC)
90043-KCCH Rhesus No Tag HEK293 Cells ≥95% (SEC-HPLC)
90043-K49H-B Rhesus His & AVI Tag HEK293 Cells ≥95% (SEC-HPLC)
10201-H08H- Human His Tag HEK293 Cells ≥95% (SDS-PAGE)
10201-H02H- Human hFc Tag HEK293 Cells ≥90% (SDS-PAGE)
10201-H05H Human mFc Tag HEK293 Cells ≥95% (SDS-PAGE)
10201-H20B1 Human His & GST Tag HEK293 Cells ≥95% (SDS-PAGE)
10201-HCCH Human No Tag HEK293 Cells ≥95% (SDS-PAGE)
80111-R02H Rat hFc Tag HEK293 Cells ≥90% (SDS-PAGE)
80111-R08H Rat His Tag HEK293 Cells ≥95% (SDS-PAGE)
90043-K02H Rhesus hFc Tag HEK293 Cells ≥90% (SDS-PAGE)

 

Featured antibodies against HER3

HER3/ErbB3 neutralizing antibody: (Cat#: 10201-MHA24)

 Cell Proliferation Induced by NRG1-β1/HRG1-β1 was Neutralized by Human ErbB3/Her3 Antibody

Cell Proliferation Induced by NRG1-β1/HRG1-β1 was Neutralized by Human ErbB3/Her3 Antibody. Image Credit: Sino Biological Inc.

Anti-HER3/ERBB3, mouse mAb: (Cat#: 10201-MM03)

 Immunofluorescence staining of Human ErbB3 in MCF7 cells

Immunofluorescence staining of Human ErbB3 in MCF7 cells. Image Credit: Sino Biological Inc.

Anti-HER3/ERBB3, rabbit pAb: (Cat#: 10201-T24)

 Immunochemical staining of human ErbB3 in human breast carcinoma

Immunochemical staining of human ErbB3 in human breast carcinoma. Image Credit: Sino Biological Inc.

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