Creative Biolabs harnesses the power of functional phage display to identify novel therapeutic targets that directly induce tumor cell apoptosis or senescence. Our Functional Phage Display Screening service is designed to move beyond simple binding and identify molecules based on their biological impact. We provide an end-to-end solution, from library construction to functional validation, accelerating the discovery of next-generation cancer therapies. Our specialized screening service for targets in tumor apoptosis and senescence enables you to:
Inducing apoptosis (programmed cell death) and senescence (irreversible growth arrest) are two cornerstone strategies in cancer therapy. Apoptosis directly eliminates malignant cells, while senescence halts their proliferation and renders them vulnerable to the immune system. However, tumors are notoriously adept at evading these cellular fates. They frequently develop mutations in key pathways, such as the p53 or Bcl-2 families, that make them resistant to conventional therapies designed to trigger cell death. The primary challenge lies in identifying novel cell surface targets that, when engaged by a therapeutic molecule, can override these resistance mechanisms and induce a cancer cell to undergo apoptosis or senescence. Traditional target discovery methods often identify proteins that are highly expressed on tumors but may not have a direct functional role in cell survival. This leads to the development of drugs that bind to cancer cells but fail to kill them effectively. A successful approach requires a screening method that directly selects for a desired biological outcome. This function-first strategy is essential for discovering next-generation therapeutics that can overcome tumor resistance and provide new hope for patients.
Fig.1 Roles of senescence and apoptosis in development and aging.1
At Creative Biolabs, we have developed a suite of services specifically tailored to discover functional molecules that modulate tumor cell fate. Our approach is centered on using carefully designed cell-based assays as the primary selection pressure during the phage display screening process. We focus on identifying candidates with real biological activity. Our key service offerings include:
Our workflow is a meticulously designed four-phase process that ensures the identification and validation of high-quality, functional candidates. Each phase is adapted to the specific goals of screening for tumor apoptosis and senescence targets.
This initial phase is critical for success. We work closely with you to define the project's precise goals. Key activities include selecting the appropriate cancer cell lines, choosing the right phage display library, and designing the custom functional screening strategy. We establish clear, measurable endpoints for apoptosis or senescence that will guide the selection process.
This is where the functional selection occurs. Instead of traditional binding-based panning on immobilized proteins, our process uses live cells. The phage library is incubated with the target cancer cells. After an appropriate time to allow for biological effects, a selection pressure is applied. For an apoptosis screen, this might involve using a reagent that only captures cells in the early stages of apoptosis. For a senescence screen, it could include sorting cells based on a senescence-specific reporter. Only the phages associated with cells undergoing the desired fate are recovered, amplified, and carried forward to subsequent rounds of increasingly stringent selection.
After several rounds of enrichment, the pool of candidate phages is analyzed to identify the specific displayed molecules. We utilize our cutting-edge Phage Display NGS Service for deep sequencing of the enriched phage population. This provides comprehensive data on the diversity and prevalence of potential candidates. Our bioinformatics team analyzes this data to identify promising sequences, cluster them into families based on consensus motifs, and prioritize them for further validation.
The most promising candidates identified by NGS are produced as soluble proteins. These molecules are then tested in a panel of functional assays to confirm their ability to induce apoptosis or senescence in the target cancer cells. We provide you with a comprehensive report containing the sequence data, binding characteristics, and functional validation results, along with the validated biologic molecules for your downstream research.
A bacteriophage is a virus that infects bacteria. It consists of a protein head that encapsulates its DNA and a tail assembly. This tail, equipped with fibers and a base plate, is a specialized structure used to recognize, attach to, and inject the phage's genetic material into a host bacterium, thereby initiating replication. Phage display is a powerful technology that uses bacteriophages to connect proteins (like antibodies or peptides) to the genes that encode them. This connection is the core principle that allows for the selection of proteins with desired functions from libraries containing billions of different variants. In phage display, a gene for a foreign protein is spliced into a phage coat protein gene. When the phage replicates, the foreign protein is "displayed" on its surface, physically linked to its own genetic blueprint inside. This makes the selection of a functional protein a simple case of identifying the phage that carries it. The technology is a true marvel; phage engineering has enabled the creation of massive molecular libraries. The genetics of these systems are well-understood, with the lambda phage genome being one of the most thoroughly studied in all of biology. The replication cycle of these viruses is also key. To understand how libraries are amplified, one can list the steps of lytic phage replication in order: attachment, penetration, biosynthesis, maturation, and lysis. This amplification step is what allows a few successful phage particles to be multiplied into a large enough population for analysis. While not directly related to tumor screening, our in-depth understanding of phage biology, including complex phenomena such as how an essential phage component induces resistance in a bacterial community, ensures that our platforms are robust, reliable, and expertly managed.
Fig.2 Typical bacteriophage diagram.
We offer a full spectrum of services and platforms to support your research from start to finish:
Choosing Creative Biolabs for your target discovery project provides a distinct competitive advantage. Our platform is built on years of expertise and a commitment to delivering functional results.
The targets and molecules discovered through our service have direct and significant applications in the development of novel cancer therapeutics.
| Application Area | Description |
|---|---|
| Monoclonal Antibody (mAb) Therapy | Identification of novel surface receptors that, when activated by a therapeutic antibody, directly trigger the caspase cascade and induce apoptosis in tumor cells. |
| Antibody-Drug Conjugates (ADCs) | Discovery of unique markers on senescent tumor cells. ADCs can target these markers to deliver a potent cytotoxic payload specifically to the non-proliferating but still dangerous cancer cells. |
| Senolytic Drug Development | By identifying targets exclusive to senescent cells, our platform enables the creation of targeted senolytic agents that can clear residual, therapy-induced senescent cells, thereby preventing tumor relapse. |
| Bispecific Antibodies | Screening for molecules that can simultaneously engage a tumor target and an immune effector cell, bringing immune-mediated killing to cells that have been pushed into a senescent state. |
| Diagnostic & Imaging Agents | The high-specificity binders discovered can be developed into tools for imaging apoptotic or senescent cells in vivo, allowing for non-invasive monitoring of treatment response. |
Our functional screening platform is designed to discover molecules that meet your special needs. Move beyond conventional target discovery and identify the biologics that can truly force cancer cells into apoptosis or senescence. Ready to discover functional targets that can redefine treatment? to discuss your project and receive a customized proposal tailored to your needs.
What kind of phage display library is best for my project?
The choice of library is critical and depends entirely on your project's goals. If you are developing a human therapeutic, a fully human antibody library (scFv or Fab) is the ideal choice to minimize immunogenicity. For discovering smaller targeting agents or mimicking natural ligands, a peptide library may be a more suitable option. Our scientific team will consult with you to analyze your specific needs and recommend the library with the highest probability of success, whether it's one of our pre-made, validated libraries or a custom-built library tailored to your unique target class.
How do you ensure that the screening actually selects for apoptosis or senescence, rather than just for binding?
This is the core of our functional screening platform. Unlike conventional methods that use purified proteins, we use live cells and select based on a biological response. For apoptosis, we can use techniques that specifically isolate cells expressing early apoptotic markers, such as Annexin V or activated caspases. For senescence, we can use FACS to sort cells based on a fluorescent reporter for senescence-associated β-galactosidase activity. This ensures that the phages we isolate are the ones causing the desired functional effect, not just the ones that bind most tightly, which is a crucial distinction for therapeutic development.
Can your platform be used to find targets on a specific cancer type or subtype?
Absolutely. Our platform is highly customizable to specific cancer types. The key is the selection of the right cell lines for the screen. We can use established cancer cell lines, patient-derived cell lines, or even genetically engineered cells that model a specific subtype or resistance mechanism. By performing subtractive panning—where the library is first depleted of binders to healthy cells—we can further enhance the specificity for targets unique to cancer cells, leading to the discovery of highly targeted and potentially safer therapeutic candidates.
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Please kindly note that our services can only be used to support research purposes (Not for clinical use).
Creative Biolabs is a globally recognized phage company. Creative Biolabs is committed to providing researchers with the most reliable service and the most competitive price.
