Creative Biolabs offers an ideal solution for Antibody-Directed Enzyme Prodrug Therapy (ADEPT). With extensive experience in antibody engineering and enzyme catalyst research, we are adept at effectively developing and screening prodrugs specifically targeting particular tumor sites. Our solutions ensure the precise release of active drugs within the tumor microenvironment, maximizing therapeutic efficacy while minimizing damage to healthy tissues.

Introduction

In the current landscape of precision antibody drug development, our preclinical CRO company can provide innovative and customized ADEPT solutions. Our team brings together extensive expertise in both antibody therapeutics and enzyme-based treatments, committed to advancing effective and safe ADEPT strategies that empower our clients to achieve breakthroughs in oncology and other critical disease areas.

We offer a comprehensive range of services, including initial drug design and optimization, thorough pharmacokinetic studies, and preclinical toxicity assessments, ensuring that each project progresses with a rigorous scientific approach. Our exclusive technological platform and unique experimental designs enable us to deliver suitable solutions throughout the entire drug development process, catering to the diverse needs of our clients.

Fig.1 Antibody-directed Enzymes for Drug Development.^1,3

Services

As a leading preclinical CRO, Creative Biolabs is dedicated to delivering high-quality research solutions to the biopharmaceutical industry, specifically on ADEPT development. Our expert team, combined with advanced technological platforms, provides a wide variety of ADEPT solutions that empower our clients to achieve breakthroughs in cancer treatment. To date, our ADEPT solutions encompass the entire process from early-stage research to preclinical trials, ensuring that every step of development is at the forefront of scientific innovation.

• ADEPT Enzyme Selection and Optimization Service

Choosing the right enzyme is key for the efficacy of ADEPT. Creative Biolabs offers comprehensive enzyme selection and optimization services, including:

Enzyme Screening and Evaluation: To meet specific client needs, we screen and evaluate suitable recombinant or natural enzymes. In vitro assays assess their catalytic efficiency and specificity.

Optimization Strategy Development: Using molecular modeling and high-throughput screening technologies, we refine the selected enzymes to enhance their stability and activity in vivo, ensuring effective conversion of prodrugs during therapy.

Functionality and Safety Assessment: Our labs conduct systematic experiments to evaluate the biological performance and compatibility of optimized enzymes, ensuring their safety and effectiveness throughout the treatment process.

• ADEPT Pre-enzyme Drugs Design Services

Leveraging our strengths in chemistry and drug design, our laboratory can develop selectively targeted pre-enzyme drug molecules. Our design services focus on:

Medicinal Chemistry Design: Our teams integrate principles of computational chemistry and medicinal chemistry to formulate prodrug structures with strong affinity, ensuring efficient conversion within the body.

Activity Validation Experiments: By establishing relevant in vitro models, we verify the activation efficacy of prodrugs in targeted tissues, confirming their biological activity for effective application.

Dosage Form and Delivery System Design: Depending on the specific therapeutic requirements, our staff designs appropriate administration routes and formulation types to enhance the bioavailability of the drugs.

• ADEPT Enzyme Prodrug Modification Service

Our ADEPT prodrug modification services are dedicated to providing clients with customized prodrug design and optimization. Our expert team employs cutting-edge chemical synthesis and bioengineering techniques to help you achieve the following objectives:

Prodrug Structure Optimization: We offer a variety of chemical modification strategies aimed at enhancing the bioavailability and efficacy of prodrugs, ensuring their stability and conversion rate within the body.

One-stop Synthesis: Based on client specifications, we provide bespoke compound synthesis, including modifications of various enzyme substrates to ensure that the resulting molecules achieve optimal targeting and release mechanisms.

Characterization Assessment: Our focus extends beyond the chemical synthesis process; we also deliver comprehensive assessments of physicochemical properties, including solubility, stability, and metabolic characteristics, to guarantee the clinical potential of the prodrugs.

• ADEPT Antibody and Pre-enzyme Drug Coupling Service

We offer state-of-the-art coupling services for antibodies and prodrugs, focusing on the design, synthesis, and optimization of antibody-drug combinations specifically for ADEPT applications.

Antibody Selection and Characterization: Based on your research requirements, we assist in selecting the most suitable antibodies and conduct thorough physicochemical characterization to ensure their efficacy and specificity in ADEPT applications.

Optimization of Coupling Reactions: We implement a range of efficient strategies to optimize coupling reactions, enhancing the covalent linkage between antibodies and prodrugs, which increases the stability and biological activity of the resulting drug.

Quality Control Testing: After coupling, we perform rigorous quality control testing on the final products, including purity analysis, concentration measurement, and activity verification, to ensure the highest quality of the end products.

• ADEPT In Vitro Experimental Services

Our ADEPT in vitro experimental services are designed to assist clients in assessing the efficacy and safety of various enzyme and prodrug combinations. The specific services we offer include:

Enzyme Activity Assays: Quantitative enzyme activity analysis in vitro to provide data support for subsequent experiments.

Cytotoxicity Testing: Using various tumor cell lines for drug sensitivity testing to determine the optimal prodrug combinations.

Drug Metabolism Studies: Evaluation of the metabolic processes of ADEPT compounds within cells to analyze their conversion efficiency into active drugs.

Mechanism of Action Studies: Employing multiple experimental techniques (such as flow cytometry and fluorescence microscopy) to investigate the cellular mechanisms of ADEPT.

Combination Therapy Evaluation: Exploring the synergistic effects of ADEPT with other anticancer agents to optimize treatment regimens and enhance anti-tumor activity.

• ADEPT Animal Model Service

For our ADEPT animal model services, we provide comprehensive experimental design and execution to ensure the effectiveness of client translational research. Our specific services include:

Selection of Animal Models: Offering a variety of tumor-bearing animal models (such as mice and rats) tailored to client research needs for the evaluation of ADEPT therapies.

Therapeutic Regimen Design: Creating well-structured ADEPT treatment plans based on actual experimental conditions, ensuring drug dosages, administration routes, and frequencies comply with preclinical research standards.

Biomarker Monitoring: Collecting and analyzing serum, tumor tissue, and other biological samples to monitor changes in biomarkers following treatment, allowing for efficacy assessment.

• ADEPT Safety and Toxicity Assessment Services

During the development of new drugs, safety, and toxicity evaluations are crucial steps. Our ADEPT safety and toxicity assessment services encompass various key areas, including but not limited to:

Non-Clinical Toxicology Studies: We provide comprehensive toxicological evaluations for lead compounds associated with ADEPT. These studies address aspects such as acute and chronic toxicity, dose-response relationships, and targeted drug effects, assisting clients in identifying potential safety concerns.

Immunogenicity Assessment: The efficacy of ADEPT treatments may be influenced by immune responses. We assess the immunogenicity of the drugs during treatment using various techniques, including ELISA and cytokine release assays, to ensure the safety of clinical trials.

Biomarker Discovery: We offer expertise in identifying biomarkers related to ADEPT therapies, facilitating early detection of possible toxicity and side effects to optimize clinical treatment strategies.

• ADEPT Pharmacokinetic and Pharmacodynamic Analysis Service

We fully recognize the crucial role that an understanding of pharmacokinetics (PK) and pharmacodynamics (PD) plays in the development of ADEPT therapies. Our services encompass the following:

Drug Metabolism Analysis: Through both in vitro and in vivo studies, we systematically evaluate the metabolic characteristics of ADEPT drugs in small animal models, providing insights into the dynamics of absorption, distribution, metabolism, and excretion (ADME).

Concentration-Effect Relationship Studies: Based on advanced bioanalytical techniques, we assess the relationship between drug plasma concentrations and therapeutic outcomes at various dosage levels, enhancing the scientific rigor and efficiency of the development process.

Customized Solutions: We design specific project protocols based on client requirements, ensuring targeted support throughout each stage of ADEPT drug development to help clients optimize therapeutic efficacy.

Data Analysis and Modeling: Employing specialized statistical tools and bioinformatics methods, we offer clients in-depth analysis and modeling of PK/PD data, aiding in the design of clinical trials.

Fig.2 Thermostability Analysis of Human GST P1-1 Prodrug Candidates.^2,3

Advantages

• Complete Experimental Design: We create customized experimental protocols based on the specific needs of our clients, ensuring that the research is both targeted and effective.
• Efficient Project Management: Our excellent project management team guarantees seamless coordination across all phases, enhancing research efficiency and reducing development timelines.
• Multiple Technology Platforms: We use the latest technologies and equipment to ensure the reliability and reproducibility of experimental data.
• Stringent Compliance: We adhere to international standards and regulations to ensure the quality and safety of each project, leading to dependable research outcomes.

Creative Biolabs offers a series of ADEPT services that encompass, but are not limited to, antibody development for specific targets, enzyme screening, and optimization, as well as prodrug design and evaluation. Our team consists of top-tier scientists with a wealth of experience in ADEPT and related technologies, allowing us to provide comprehensive support to our clients, from proof of concept to preclinical ADEPT studies. We warmly invite all our clients to contact us to explore how our ADEPT solutions can advance your research and development projects.

References

1. Romei, Matthew G., et al. "Antibody-guided proteases enable selective and catalytic degradation of challenging therapeutic targets." Journal of Biological Chemistry 299.5 (2023).
2. Ismail, Aram, Sridhar Govindarajan, and Bengt Mannervik. "Human GST P1-1 Redesigned for Enhanced Catalytic Activity with the Anticancer Prodrug Telcyta and Improved Thermostability." Cancers 16.4 (2024): 762.
3. Distributed under Open Access license CC BY 4.0, without modification.

For Research Use Only | Not For Clinical Use