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Discovering Novel Anti-Angiogenesis & Anti-Metastasis Targets Using Phage Display

Introduction Services Workflow Phage Display Highlights Applications FAQs Resources Related Sections

Creative Biolabs offers a specialized service to discover novel biologics that actively inhibit tumor angiogenesis and metastasis. We go beyond simple binding to identify functional molecules that block the critical pathways tumors use to grow, spread, and survive. This is achieved through our advanced approach to Functional Phage Display Screening, a robust methodology focused on isolating molecules based on their desired biological effect, not just their affinity. Our powerful screening platform enables:

  • The discovery of antibodies or peptides capable of preventing new blood vessel formation.
  • The identification of molecules that successfully block cancer cell migration and invasion.
  • To find novel cell surface targets on endothelial or metastatic tumor cells.

The Scientific Challenge of Tumor Growth & Spread

A tumor cannot grow beyond a minimal size without a dedicated blood supply. This process, known as angiogenesis, involves the formation of new blood vessels from existing ones. These new vessels supply the tumor with oxygen and nutrients, allowing it to expand. Furthermore, this vascular network provides a route for cancer cells to escape the primary tumor and travel to distant sites in the body, a process called metastasis. Metastasis is the primary cause of mortality in cancer patients. he central challenge in developing effective anti-angiogenic and anti-metastatic therapies is identifying targets that are not just present but functionally essential to these processes. Many proteins are overexpressed on the surface of endothelial cells in the tumor microenvironment or on metastatic cancer cells. However, simply targeting these proteins does not guarantee an inhibitory effect. A therapeutic molecule must actively block a critical function, such as receptor signaling that drives cell migration, or the adhesion molecules that allow a cancer cell to invade new tissue. Traditional target discovery methods often fall short because they select for high-affinity binders without regard for function. This can lead to the development of drug candidates that bind beautifully to their target but do nothing to stop the cancer's progression. To overcome this, a screening approach is needed that directly selects for molecules capable of inhibiting the cellular machinery of angiogenesis and metastasis.

Fig.1 A diagram illustrating the process of tumor angiogenesis, showing how a tumor microenvironment triggers abnormal blood vessel growth that ultimately promotes cancer growth and metastasis. (OA Literature)Fig.1 The role of tumor angiogenesis in cancer growth and metastasis

Our Anti-Angiogenesis & Anti-Metastasis Services

Creative Biolabs has engineered a suite of services dedicated to the discovery of functional inhibitors of tumor progression. We use sophisticated, physiologically relevant cell-based assays as the foundation of our screening campaigns, ensuring that the candidates we identify possess real, measurable biological activity. Our focus is on delivering results, not just data. Our specialized service offerings include:

  • Anti-Angiogenesis Target/Inhibitor Discovery: We screen vast phage libraries on endothelial cells (like HUVECs) to identify antibodies or peptides that directly inhibit key steps of angiogenesis. This includes screens designed to block endothelial cell proliferation, migration, or tube formation in matrigel assays.
  • Anti-Metastasis Target/Inhibitor Discovery: This service focuses on the cancer cells themselves. We perform functional screens to discover molecules that prevent cancer cell invasion through extracellular matrix barriers or block their adhesion to endothelial layers, mimicking the process of extravasation.
  • Tumor Vasculature-Homing Molecule Identification: Using in vivo phage display, we can identify peptides and antibodies that specifically home to the unique vascular signatures of tumors. These molecules are invaluable for developing targeted drug delivery systems, such as antibody-drug conjugates (ADCs), that concentrate therapeutic payloads directly at the tumor site.
  • Pathway-Specific Inhibitor Screening: Our assays can be tailored to find molecules that disrupt specific signaling pathways known to be critical for angiogenesis and metastasis, such as the VEGF/VEGFR or HGF/c-MET axes. This approach delivers candidates with a known mechanism of action, accelerating downstream development.

Our Functional Screening Workflow

Our process is a rigorous, four-phase workflow designed to systematically identify, analyze, and validate functional inhibitors of angiogenesis and metastasis. Each phase is customized to address the unique challenges of these complex biological processes.

Phase 1: Project Initiation & Preparation

Success begins with a solid plan. In this phase, we collaborate with you to meticulously design the project. This involves selecting the most appropriate cellular models, such as primary human endothelial cells (HUVECs) for angiogenesis studies or highly aggressive, metastatic cancer cell lines for invasion assays. We then define the functional selection criteria and choose the optimal phage display library to maximize the potential for discovering novel candidates.

Phase 2: Functional Screening & Enrichment

This is the core of our function-first approach. The phage library is applied to the cellular model, and a selection pressure is introduced that favors phages displaying molecules with the desired inhibitory function. For example, in an anti-migration screen, only the phages that successfully prevent cells from moving across a barrier are collected. In an anti-angiogenesis screen, phages that inhibit the formation of capillary-like structures in a tube formation assay are selected. Through multiple rounds, we enrich for a population of phages that actively block the biological process of interest.

Phase 3: Data Generation & Analysis

Once the enrichment is complete, we must identify the successful candidates. We employ our specialized Phage Display NGS Service to perform deep sequencing on the enriched phage pool. This powerful technique provides a comprehensive digital census of all potential hits, revealing their sequences and relative abundance. Our bioinformatics experts then analyze this wealth of data to identify consensus sequences, group candidates into families, and prioritize the most promising clones for validation.

Phase 4: Validation & Delivery

The most promising sequences identified by NGS are converted into soluble antibodies or peptides. These purified molecules are then subjected to a battery of functional validation assays. We confirm their ability to inhibit endothelial tube formation, block cancer cell invasion in transwell assays, or prevent cell migration in wound-healing assays. You receive a final report with all sequence and functional data, along with the validated molecules themselves, ready for your next stage of research.

Understanding Phage Display Technology

So, what is phage display? It is a laboratory technique that uses bacteriophages—viruses that infect bacteria—to study protein-protein, protein-peptide, and protein-DNA interactions. Essentially, bacteriophages are viruses that have been repurposed as powerful tools for discovery. This phage virus system allows us to create a physical link between a protein of interest and the gene that encodes it. A gene for a protein we want to study is inserted into a gene for a phage's coat protein. The genetic instructions remain safely inside. This allows scientists to screen huge libraries of different proteins and, when they find one with the desired function, easily identify its genetic code from the phage carrying it. The robust nature of these viruses is well-studied, with the structure of phage T4 being a classic example of complex viral architecture. While some research explores using bacteriophages as antibiotics to fight bacterial infections, particularly the lytic phage type that ruptures host cells, in biotechnology, we primarily use them as a display and selection tool.

Our Full Suite of Phage Display Services & Platforms

We offer an integrated ecosystem of services and platforms designed to support every phase of your discovery project. Our foundational Phage Display Service encompasses the entire workflow, starting with the creation of high-quality libraries through our Phage Display Library Construction service and the development of tailored Phage Display System Construction. For any unique challenge, our Custom Services Based on Phage Display team is ready to design a bespoke solution.

Our core expertise lies in Phage Display Library Screening and Biopanning, which we execute across our versatile Phage Display Screening Platforms. These platforms are tailored for different biological questions:

Advantages of Our Functional Screening Service

Partnering with Creative Biolabs provides unparalleled advantages for your anti-angiogenesis and anti-metastasis research.

  • Function-First Approach: Our core philosophy is to select for biological function. We design our screens to find molecules that do something, not just bind to something. This dramatically increases the therapeutic potential of the candidates we deliver.
  • Expert Scientific Support: Our team consists of Ph.D. scientists with extensive experience in cancer biology, vascular biology, and phage display technology. They work with you as strategic partners to design and execute the best possible project.
  • Physiologically Relevant Models: We use primary cells (like HUVECs), co-culture systems, and 3D models to mimic the tumor microenvironment as closely as possible, ensuring the targets we identify are relevant to human disease.
  • High-Throughput Validation: We have developed a suite of automated, high-throughput functional assays to rapidly validate hundreds of potential candidates, allowing us to quickly confirm their inhibitory activity and focus on the most promising leads.

Applications In Oncology Drug Development

The functional inhibitors and novel targets discovered through our service pave the way for a new generation of cancer therapies designed to control tumor progression. Rather than focusing solely on killing cancer cells, these strategies aim to contain the disease by cutting off its supply lines and blocking its escape routes.

Developing Vascular Disrupting Agents (VDAs)

Our platform can identify antibodies or peptides that bind specifically to the surface of tumor-associated endothelial cells. These targeting moieties can then be used to create potent VDAs. Unlike traditional anti-angiogenics that prevent new vessel growth, VDAs are designed to attack and destroy the existing tumor vasculature. By using a tumor-homing molecule discovered via our screens as a delivery vehicle for a potent toxin or pro-coagulant factor, it is possible to induce rapid vascular collapse within the tumor, leading to widespread cancer cell death due to starvation.

Creating Potent Anti-Metastatic Therapeutics

Metastasis is a multi-step process involving cell detachment, invasion, intravasation, and extravasation. Our functional screens can identify biologics that inhibit any of these critical steps. For example, we can discover an antibody that blocks the function of an integrin required for cell migration, effectively immobilizing the cancer cells. Such a molecule could be developed as a standalone therapy to prevent the spread of cancer in high-risk patients or used in combination with conventional chemotherapy to treat both the primary tumor and prevent the formation of new metastatic colonies.

Enhancing Drug Delivery and Imaging

The peptides and antibodies that specifically home to tumor vasculature or metastatic niches are exceptionally valuable tools for targeted delivery. These molecules can be conjugated to nanoparticles, liposomes, or even radioactive isotopes. This creates sophisticated drug delivery systems that concentrate a therapeutic payload directly at the site of disease, maximizing its efficacy while minimizing systemic side effects. The same homing molecules can be adapted for diagnostic purposes, enabling non-invasive imaging that can track the progression of metastasis or monitor a tumor's response to anti-angiogenic therapy in real-time.

Control tumor progression by striking at its lifelines. Our functional phage display screens are engineered to identify potent biologics that actively inhibit angiogenesis and metastasis. Stop searching for binders and start discovering functional inhibitors that can contain and control cancer. Take the next step in developing transformative cancer therapies. Contact our experts at Creative Biolabs to begin your project and request a detailed quote.

FAQs

What cell models do you use for anti-angiogenesis screening?

We primarily use Human Umbilical Vein Endothelial Cells, as they are a well-established and reliable model for studying the fundamental processes of angiogenesis. They can be induced to proliferate, migrate, and form capillary-like tubes in culture. For more specific projects, we can also use other primary endothelial cells or cell lines. We can develop co-culture systems with tumor cells or fibroblasts to better replicate the complexity of the tumor microenvironment and ensure the highest physiological relevance for your target discovery program.

How is your functional screen different from a standard biopanning experiment against a purified protein?

A standard biopanning experiment selects for binding affinity against a single, isolated protein on a plastic plate. Our functional screen uses live cells and selects for a biological outcome. For instance, instead of finding what binds to VEGFR2, we see what stops endothelial cells from forming tubes, regardless of the target. This function-first approach can uncover inhibitors of known targets, inhibitors of entirely new targets, or even allosteric modulators that work in unexpected ways.

What are the final deliverables for a project?

Upon completion of a project, we provide a comprehensive package that equips you for the next steps in your research. This includes the full DNA and amino acid sequences of all validated lead candidates, a detailed report of the NGS data and bioinformatic analysis, and robust data from the functional validation assays. Crucially, we also deliver purified, soluble samples of the lead antibody fragments or peptides for you to perform your own in-house experiments.

Reference:

  1. Ayoub, Nehad M., et al. "Targeting angiogenesis in breast cancer: current evidence and future perspectives of novel anti-angiogenic approaches." Frontiers in pharmacology 13 (2022): 838133. Distributed under Open Access license CC BY 4.0, without modification. https://doi.org/10.3389/fphar.2022.838133

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