Antibody-Directed Enzyme Prodrug Therapy (ADEPT) has emerged as a powerful treatment approach, effectively targeting cancer cells and minimizing damage to healthy cells. To ensure the safety and efficacy of ADEPT, Creative Biolabs offers a wide collection of ADEPT safety and toxicity assessment services, providing clients with comprehensive and detailed support for their ADEPT study needs.

Introduction

In recent years, Creative Biolabs has performed comprehensive pharmacokinetic (PK) and pharmacodynamic (PD) studies, thoroughly evaluating the distribution, metabolism, and excretion profiles of antibody drugs within the body. This information assists researchers in determining the most suitable dosage and administration regimens. Additionally, CROs provide both long-term and short-term toxicological assessments, including acute, subacute, and chronic toxicity studies, to fully evaluate the potential effects of the drug on various organs, thereby ensuring the safety of clinical trials.

Fig.1 Monoclonal Antibody-based Therapies.^1,3

In terms of drug carriers or solvents, Creative Biolabs conducts safety evaluations to ensure these components do not trigger adverse reactions. Simultaneously, immunogenicity assessments are a critical task for our labs, as they analyze the impact of antibodies on the host's immune system, identifying potential risks such as allergic reactions or autoimmune diseases. Furthermore, Creative Biolabs evaluates the specificity of antibody binding to target proteins, ensuring that the antibody drugs can accurately target tumor cells while minimizing effects on normal cells, which helps to reduce toxicity.

Finally, Creative Biolabs utilizes advanced in vitro and animal models to simulate human responses for toxicity evaluations, to effectively reduce the number and complexity of animal experiments, thus further advancing research on drug safety and efficacy.

Services

To support our worldwide clients, Creative Biolabs has launched well-mature ADEPT safety and toxicity assessment services, which include two essential modules: the ADEPT acute and chronic toxicity testing and the ADEPT immunogenicity analysis. We are dedicated to safeguarding your ADEPT development journey.

ADEPT Acute and Chronic Toxicity Testing Service

In the development of Antibody-Directed Enzyme Prodrug Therapy (ADEPT), toxicity assessment plays a crucial role in ensuring drug safety. We offer clients rapid and precise toxicity evaluations. We employ state-of-the-art experimental models and advanced techniques, incorporating a range of dosage gradients, to carry out an in-depth assessment of a drug's impact on biological systems. By conducting thorough toxicological analyses, we deliver detailed data to our clients, enabling them to pinpoint any potential toxic responses. This methodology not only reduces the risks associated with research and development but also bolsters the reliability of subsequent clinical trials, ultimately improving your product's competitive edge in the market.

ADEPT Immunogenicity Analysis Service

During the development of antibody-directed therapies, immunogenicity is a critical factor influencing both the efficacy and safety of the drug. Our ADEPT immunogenicity analysis services are designed to evaluate the potential risks of immune reactions triggered by the drug. Following internationally recognized best practices, we employ a range of cutting-edge techniques, including ELISA, flow cytometry, and high-throughput screening, for an in-depth analysis of immunogenicity in ADEPT. Our team will develop customized immunogenicity assessment strategies tailored to the specific characteristics and intended use of each drug, ensuring thorough testing results. Additionally, we provide clients with detailed reports and recommendations to help them understand potential immunological risks and bolster their clinical development efforts.

Fig.2 Cell Viability Analysis of Different Concentrations of PDT-MIONP/Prodrug System in HeLa Cells.^2,3

Process

1. Acute Toxicity Assessment

Animal Selection: Using healthy C57BL/6 mice, dividing them into an experimental group and a control group, with 10 mice in each group.

2. Antibody Selection and Optimization

- Utilize in vitro screening and affinity maturation techniques to select and optimize antibodies that exhibit high specificity and affinity for specific tumor antigens.

- Apply structural biology methods to elucidate the binding mechanisms between antibodies and antigens, guiding antibody engineering modifications. Antibody-Directed Enzyme Prodrug

3. Screening of Enzyme Prodrugs

- Screen enzyme prodrug compounds to identify those suitable for conjugation with antibodies.

- Conduct an initial assessment of potential toxicity through analysis of the drug's mechanism of action and target identification.

4. Cell Model Assessment

- Perform in vitro toxicity assays to evaluate the selective toxicity of antibody-directed enzyme prodrugs against tumor cells.

- Compare results with various normal cell lines to determine the selectivity for normal cells.

5. Immunogenicity Evaluation

- Assess the immunogenic potential of the antibody-directed enzyme prodrugs using techniques such as ELISA and Western Blot to examine interactions with the immune system.

6. Animal Model Studies

- Select appropriate mouse or rat models for animal studies to evaluate the pharmacokinetics and tumor-targeting efficacy of the antibody-directed enzyme prodrugs.

- Continuously monitor clinical signs and physiological indicators in the animals to promptly assess any potential toxic reactions.

7. Adverse Effects and Toxicity Testing

- Administer varying doses of the antibody-directed enzyme prodrugs and observe the toxicity responses in the animal models over different time intervals, including acute, subacute, and chronic toxicity.

- Regularly perform hematological and biochemical tests to assess the impact of the drug on the liver, kidneys, and other organs.

Advantages

The preclinical assessment of the safety and toxicity of ADEPT is not only a crucial step in ensuring treatment efficacy and safety, but it is also a necessary measure to comply with regulatory standards. Therefore, Creative Biolabs has established a platform for evaluating the safety and toxicity of ADEPT, focusing on its effects on normal tissues to minimize the risk of adverse side effects.

Nowadays, we conduct comprehensive toxicity testing on ADEPT components, such as antibodies and enzymes, to identify any potential toxic reactions. Our scientists can analyze systemic toxicity linked to various dosing regimens, providing a scientific basis for optimizing ADEPT treatment plans for clients. Our data can further assist clients in determining safe and effective dosages, ultimately enhancing the effectiveness of future clinical outcomes.

• High Precision: Our assessment services utilize both in vitro and in vivo experiments to ensure the targeting efficacy and selectivity of antibodies, thereby minimizing potential toxicity.
• Multi-tiered Analysis: Creative Biolabs employs a comprehensive approach that integrates cellular-level studies, animal models, and preclinical research data to evaluate drug biodistribution, metabolic pathways, and associated cytotoxicity across multiple systems.
• Real-time Monitoring: With the use of advanced biomarkers and imaging techniques, CBL is capable of continuously monitoring pathological changes during treatment, allowing for a more sensitive capture of the drug's dynamic responses within the body.
• Robust Data Integration: By leveraging big data analytics and artificial intelligence algorithms, our team can extract valuable insights from complex datasets, identify potential safety concerns, and enhance the scientific rigor and reliability of our evaluations.

At Creative Biolabs, our ADEPT safety and toxicity assessment services encompass various aspects, including the evaluation of drug biocompatibility, pharmacological studies, and toxicological analysis. We warmly invite research and development teams, and relevant customers to contact us for collaborative discussions on the ADEPT future and potential.

References

1. Sharma, Prerna, et al. "Therapeutic antibodies in medicine." Molecules 28.18 (2023): 6438.
2. Pérez, Elena, et al. "Novel Directed Enzyme Prodrug Therapy for Cancer Treatment Based on 2'-Deoxyribosyltransferase-Conjugated Magnetic Nanoparticles." Biomolecules 14.8 (2024): 894.
3. Distributed under Open Access license CC BY 4.0, without modification.

For Research Use Only | Not For Clinical Use