Next-IO™ HER3 Therapeutic Monoclonal Antibody Program
About This Program
This program aims to develop HER3 therapeutic monoclonal antibody for colorectal cancer immunotherapy.
Rationale for our program:
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The therapeutic potential of HER3 has received attention in recent years as it is a key heterodimeric partner for other EGFR family members and has the potential to modulate EGFR/HER2 mediated resistance.
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Studies have shown that HER3 is up-regulated in several malignancies including colorectal cancer (CRC) and promotes tumor progression through interaction with different receptor tyrosine kinases (RTKs).
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Studies have also shown that HER3 is significantly associated with treatment failure, mainly through regulation of PI3K / AKT, MAPK / ERK, and JAK / STAT signaling pathways
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Furthermore, activating mutations in HER3 suggests a potential for HER3 as a direct therapeutic target.
These findings indicate an important role for HER3 in CRC progression and metastasis.
HER3
HER3 belongs to the human epidermal growth receptor (EGFR/HER) family and is composed of four members (EGFR / ERBB1 / HER1, ERBB2 / HER2 / Neu, ERBB3 / HER3 and ERBB4 / HER4). HER3 is widely expressed in numerous cells, such as epithelial cells, nerve cells, tumor cells, and mesenchymal cells. HER3 is known to regulate cellular processes such as cell division, cell proliferation, differentiation, angiogenesis, and tumor progression. There is a variety of evidence that HER3 overexpression reduces survival in patients with colorectal cancer, and the mechanism of occurrence is shown in figure 1.
Fig.1 HER3 overexpresses and reduces survival in patients with colorectal cancer. (Gespach, 2012)
Supporting Data
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Anit-HER3 antibody (KTN3379) preferentially suppresses tumor growth in colorectal cancer model HT29.
(Xiao, 2016)
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Inhibition of HER3 with AZD8931 (AZD) significantly blocked EC CM-induced colorectal tumor growth.
(Wang, 2019)
These data support the rationale for the development of the first-in-class human HER3 Abs with an improved therapeutic index for the treatment of colorectal cancer.
Colorectal cancer
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Colorectal cancer is the most common type of gastrointestinal cancer, and its incidence is increasing in developed countries.
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The global cancer immunotherapy market is worth $58.1 billion in 2018. The expanding research of immunotherapy will become one of the important trends in the global colorectal cancer treatment market from 2019 to 2023.
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Immunotherapy products such as immunological checkpoint inhibitors and vaccines are part of active research.
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The global colorectal cancer treatment market research report predicts that the market will grow at a compound annual growth rate of more than 8% during the forecast period.
Ongoing Clinical Trials
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Currently, several therapeutic antibodies against HER3 are being investigated in clinical and preclinical studies. However, no antibodies have been approved by the FDA.
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Recent studies have also found that HER3 bispecific antibodies, such as EGFR / HER3 or HER2 / HER3, have been shown to have potent anti-tumor effects in both laboratory and clinical studies. In an effort to optimally leverage HER3-mediated immune response, our next-IO™ HER3 targeted antibody program attempts to explore the optimal dual-targeted combination therapy by involving other immunomodulatory agents.
(Liu, 2019)
Program Plan
We have extensive knowledge of end-to-end program development. For each program, we are committed to delivering the final complete program to our clients within 1.5 years before entering the IND stage.
Cooperation
Creative Biolabs is looking for potential partners (include but not limit to major pharma or biotech firms) to develop HER3 therapeutic monoclonal antibody program together. Our scientists are dedicated to bringing years of valuable experience to our partner and achieve a meaningful partnership together. For any partners interested in our Next-IO™ programs, Creative Biolabs welcomes collaboration.
Here are two ways for your choice, and please contact us for more details.
1) Collaborate with us and co-develop the programs from the discovery phase to IND enabling. Costs will be shared.
2) Become a licensed candidate for our programs.
With our quality control protocol and knowledge of global regulatory requirements, we can help our partners further their programs with more chances to succeed. Look forward to cooperating with you in the near future.
References
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Gespach, C.; et al. Increasing potential of HER3 signaling in colon cancer progression and therapy. Clinical Cancer Research An Official Journal of the American Association for Cancer Research. 2012, 18(4):917.
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Liu X.; et al. Development of effective therapeutics targeting HER3 for cancer treatment. Biological Procedures Online. 2019, 21(1): 1-10.
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Wang, R.; et al. Endothelial cells promote colorectal cancer cell survival by activating the HER3-AKT pathway in a paracrine fashion. Molecular cancer research. 2019, 17(1): 20-29.
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Xiao, Z.; et al. A potent HER3 monoclonal antibody that blocks both ligand-dependent and-independent activities: differential impacts of PTEN status on tumor response. Molecular cancer therapeutics. 2016, 15(4): 689-701.
For Research Use Only | Not For Clinical Use