About This Program
This program aims to develop COX2 therapeutic monoclonal antibody for immuno-oncology.
Cyclooxygenase-2 (COX-2) produces cancer stem cell (CSC)-like activity and is involved in cancer apoptosis, proliferation, angiogenesis, inflammation, invasion and metastasis of cancer cells. Especially, COX-2 weighs heavily in the occurrence and promotion of carcinogenic cell resistance because inhibition of COX-2 increases its sensitivity to chemical and radiation therapy. Some major upstream regulators of COX-2 are the MAPK family, EGFR and nuclear factor-kappa beta (NF-κB). COX-2 targeting antibodies can be used as effective adjuvants to chemotherapeutic drugs, providing a promising strategy for next-generation combination therapies.
COX2
COX-2 is released by cancer-associated fibroblasts (CAFs), macrophage type 2 (M2) cells, and other cancer cells to the tumor microenvironment (TME). Other research data is highlighted:
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Overexpression of COX-2 is associated with epithelial-mesenchymal transition (EMT) and lymph node metastasis.
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COX-2 mediates TME hypoxia and its positive interaction with YAP1 and anti-apoptotic media are favorable.
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COX-2 can enhance cancer cell resistance to chemotherapeutic drugs.
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COX-2 exerts most of its functions by metabolizing anandamide into prostaglandin E2 (PGE2) ethanolamide.
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In some limited cases, COX-2 also acts as an anti-tumor enzyme.
Fig.1 A diagram revealing multitasking roles for COX‐2 in the promotion of cancer.1
COX2 in Cancer Studies
Here are some published data about COX2 working as a potential target for cancer immunotherapy. From these specifics, COX-2 is a marker indicator to poor prognosis and can stimulate cancer progressions. Inhibition of COX-2 may provide a promising approach to cancer treatment, especially by working as an adjuvant to other suitable chemotherapeutic agents.
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The high expression on both c-Myb and COX-2 are significantly associated with shorter overall survival rate in stage II and stage III colorectal cancer patients treated with 5-fluorouracil (5-fu).
Fig.2 The influence of c-Myb and COX-2 expression for overall survival in CRC.2
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High expression level of COX-2 in the BRAF mutation state may link to poor prognosis of colorectal cancer.
Fig.3 Kaplan-Meier analysis of colorectal cancer-specific survival according to tumour COX-2 expression status in strata of BRAF mutation status.3
Indication
In normal tissues, production of COX-2 is almost indistinguishable. However, it is expressed in many tumor-generating agents, including adenocarcinoma, squamous cell carcinoma (SCC), cholangiocarcinoma, transitional cell carcinoma, and hepatocellular carcinoma. Data have shown the tumor microenvironment (TME) may also be an inducer to COX-2 overexpression. In this case, our project will focus on developing COX-2 specific antibodies for tumor diagnosis.
Ongoing Clinical Trials
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Currently, no anti-COX-2 antibodies are used in tumor prognosis and diagnosis.
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In this case, it is still a compelling target for cancer immunotherapy. In an effort to optimally leverage COX2-mediated immune response, our next generation of COX2 targeting treatment attempts to explore a combination strategy- that is, how to exert greater anti-tumor effects by working with other suitable chemotherapeutic agents.
Program Planning and Management
We have extensive knowledge of end-to-end program development. For each program, we are committed to delivering the completed program to our clients within 1.5 years before entering the IND stage.
Fig.4 Project pipeline management of therapeutic monoclonal antibody.
Cooperation
Creative Biolabsis looking for potential partners (include but not limit to major pharma or biotech firms) to develop COX2 therapeutic Monoclonal Antibody program together. Our scientists are dedicated to bringing years of valuable experience to our partner and achieve a meaningful partnership. For any partners interest 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 advance their programs with more chance to succeed. Look forward to cooperating with you in the near future.
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