In the past decade, Creative Biolabs practices and has gained rich experience in antibody discovery, engineering, in vitro evaluation, in vivo assessment, etc. Now we are hoping to extend our experience on Next-IO™ programs, with a hope to co-develop the therapeutic antibody drug pipelines with trustful partners. We are dedicated to forwarding the progress to the pre-IND stage in an effective manner. This program aims to develop the therapeutic monoclonal antibody (mAb), specifically, against cadherin.

Cadherin

Cadherin is a family of critical adhesion molecules involving in cell-cell adhesion, junction formation, and tissue morphogenesis. There are several members in the family, to name, E-cadherin, N-cadherin, and R-cadherin. In epithelial cells, E-cadherin is essential for cell-cell interaction maintenance and maintaining the balance of polarized epithelial monolayers. E-cadherin is the important ligand for KLRG1, a critical immune checkpoint expressed on NK cells (see Fig.1). Their interaction promotes tumor progression. Studies also indicatedthe98 loss of E-cadherin function is strongly associated with cancer progression.

Relevance to Cancer

Among all the cancer types that experience the loss of E-cadherin expression, it’s demonstrated that activating monoclonal antibody against E-cadherin can significantly decrease the lung metastasis. Another study indicated that soluble E-cadherin is highly expressed in ovarian cancer patients and may be correlated with angiogenesis. These data imply E-cadherin has the potential to become a therapeutic target in cancer treatments. In addition, N-cadherin, another member of cadherin, is highly expressed in colorectal cancer (CRC), which suggests its potential therapeutic role in treating CRC. In summary, cadherin relates to tumor invasion, metastasis, and tumorigenesis, and targeting cadherins may be a promising approach to inhibit tumor progression.

Our Anti-Cadherin Antibody Program

Our anti-Cadherin mAb program aims to develop the novel therapeutic mAb against different Cadherin members for cancer treatment. We propose three following pathways for your choice.

• Activate monoclonal antibody against E-cadherin to treat lung cancer,
• Inhibit monoclonal antibody against soluble E-cadherin to treat ovarian cancer,
• Inhibit monoclonal antibody against N-cadherin to treat colorectal cancer.

Except for monoclonal antibody, we also focus on combination strategies, or other antibody modalities, such as bispecific antibody, etc. to cover the full spectrum of cancer immunotherapies targeting cadherins. If you have interests, please feel free to reach out to our scientists for further consultation.

Published Data

• N-cadherin is highly expressed in CRC patients.
• High expression of N-cadherin is correlated with poor prognosis in patients with CRC.
• N-cadherin inhibition can downregulate the proliferation and migration of tumor cells.

Based on these data, N-cadherin is shown to be a potential target to treat CRC and blocking N-cadherin (alone or in combination with other treatments) maybe a promising immunotherapeutic strategy to treat CRC.

Program Planning and Management

We have extensive experience in performing comprehensive program developments and effective problem-solving. For our Next-IO™ programs, we are committed to delivering the program to the pre-IND stage within about 1.5 years. Accurate timeline will be determined on a case-by-case basis. Here is a draft timeline for your glance.

Fig.1 The timeline of Next-IOᵀᴹ programs.

Collaboration

Creative Biolabs is seeking potential partners to co-develop the cancer immunotherapies targeting different members of cadherins. Equipped with state-of-the-art facilities, our team is dedicated to providing end-to-end drug discovery and development programs. Our unique Next-IO™ programs will surely unleash the creative spirit and achieve significant success in the field of immuno-oncology. Please contact us to learn how we can collaborate further.

References

• Nakamura, Seiko, et al. "Molecular basis for E-cadherin recognition by killer cell lectin-like receptor G1 (KLRG1)." Journal of Biological Chemistry 284.40 (2009): 27327-27335.
• Petrova, Yuliya I., Leslayann Schecterson, and Barry M. Gumbiner. "Roles for E-cadherin cell surface regulation in cancer." Molecular biology of the cell 27.21 (2016): 3233-3244.
• Rangarajan, Sneha, and Roy A. Mariuzza. "Natural Killer Cell Receptors." Structural Biology in Immunology. Academic Press, 2018. 101-125.
• Tang, Maggie KS, et al. "Soluble E-cadherin promotes tumor angiogenesis and localizes to exosome surface." Nature communications 9.1 (2018): 2270.
• Yan, Xuebing, et al. "N-cadherin, a novel prognostic biomarker, drives malignant progression of colorectal cancer." Molecular medicine reports 12.2 (2015): 2999-3006.
• Albrecht, Lauren V., Kathleen J. Green, and Adi D. Dubash. "Cadherins in cancer." The Cadherin Superfamily. Springer, Tokyo, 2016. 363-397.

For Research Use Only | Not For Clinical Use