Food Science and Environmental Health Laboratory Report

Categories: Biology

Report, Pages 4 (776 words)

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Chosen Compound: Durvalumab (MED14736)

The humanised antibody therapy compound under investigation is Durvalumab (MED14736), a monoclonal antibody designed to inhibit PD-L1 function, thereby stimulating the immune system to target and destroy cancerous cells. PD-L1 negatively regulates immune function in cancer and inflammatory diseases by interacting with the PD-1 receptor on T-Cells. Preventing the binding of PD-L1 to T-Cells is essential to maintain their function (OncoLink Team, 2019).

Durvalumab, also known commercially as Imfinzi, is a Human IgG1k monoclonal antibody approved for the treatment of various cancers, including Urothelial Carcinoma and Non-Small-Cell Lung Carcinoma (NSCLC).

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It is produced by MedImmune, AstraZeneca, and Celgene.

Pre-Clinical Testing

According to Pfizer (2019), only a small fraction of molecules undergoing testing become therapeutic drugs, highlighting the rigorous pre-clinical and clinical trials required to ensure safety and efficacy. Experimental pharmacology aims to assess the effects, efficacy, and toxicity of pharmacological agents in various species.

Pre-clinical Testing Methods

In Silico Testing

In Silico, or computer-based experimentation, serves as the initial step in evaluating a new compound.

It involves the use of computational models and data integration to analyze biological and medical data globally (Ekins, Mestres, & Testa, 2007). In Silico methods facilitate the creation of models, simulations, predictions, and hypotheses, streamlining drug discovery.

In Vitro Testing

In Vitro testing, conducted in controlled environments using isolated live cells, assesses the efficacy of a compound (Franks, T., 2018). While it is time and cost-effective and provides relevant results using human cells, it lacks information on side effects and toxicity.

In Vivo Testing

In Vivo testing, conducted in live animals, determines drug safety and toxicity before human trials (Franks, T.

, 2018). While reliable and specific, it is costly and time-consuming and must comply with strict ethical standards.

In Vitro Testing for Durvalumab

Based on the European Medicines Agency (Imfinzi Assessment Report), the following In Vitro tests are suitable for Durvalumab:

Binding Affinity and Specificity: Analyze sequence homology and confirm high binding affinity to human PD-L1.
Confirmation of Durvalumab's inhibition of PD-L1 and PD-1 interaction and its ability to overcome PD-L1-mediated inhibition of T Cells in Vitro.
Confirmation that Durvalumab does not inhibit antigen-presenting cells or trigger effector function.
Assessment of cytokine release induced by Durvalumab in combination with tremelimumab.
Evaluation of Durvalumab's potency using primary T cells from different donors.

In Vivo Testing for Durvalumab

Suitable In Vivo tests for Durvalumab, based on the Imfinzi Assessment Report, include:

In Vivo murine models of human cancer using mice to assess tumor growth inhibition.
Evaluation of dose-dependent anti-tumor activity in a mouse colorectal cancer model.
Combination testing of anti-mouse PD-L1 antibody with oxaliplatin or anti-mouse antibody.

Toxicity Testing

Toxicity testing is an integral part of In Vivo testing to assess adverse effects on living organisms. Key toxicity tests include:

Dermal Toxicity
Subchronic Toxicity
Reproductive Toxicity
Teratogenicity
Perinatal/Postnatal Toxicity
Mutagenicity

Clinical Trials

Clinical trials for Durvalumab and similar drugs typically consist of three phases:

Phase 1: Involves testing the drug in a small number of patients to assess immediate effects.
Phase 2: Encompasses a larger sample size (100+ candidates) to evaluate short-term side effects, assess risks, and measure efficacy.
Phase 3: Expanded trials (100-1000 patients) provide more data on safety, efficacy, and side effects. Double-blind testing is often employed.

Once sufficient data is collected and the drug is deemed safe, it can proceed to market release.

Results and Discussion

The results of pre-clinical testing are crucial in determining the safety and efficacy of Durvalumab. In Silico testing provided valuable insights into the compound's potential, helping identify promising areas for further research.

In Vitro testing confirmed Durvalumab's binding affinity to PD-L1 and its ability to inhibit PD-L1 and PD-1 interaction, making it a potential candidate for immunotherapy.

In Vivo testing using murine models demonstrated the compound's anti-tumor activity in various cancer types, further supporting its potential as a therapeutic agent.

Toxicity testing is ongoing, and results will provide critical information about potential adverse effects on living organisms.

Conclusion

The pre-clinical testing of Durvalumab has shown promising results in terms of its efficacy in inhibiting tumor growth and its potential as an immunotherapy agent. Further research and clinical trials are needed to confirm its safety and effectiveness in humans. If successful, Durvalumab could offer new hope in the treatment of various cancers.

References

1. OncoLink Team. (2019). The PD-1/PD-L1 Pathway in Cancer. OncoLink. https://www.oncolink.org/cancer-treatment/immune-therapy/the-pd-1-pd-l1-pathway-in-cancer

2. Ekins, S., Mestres, J., & Testa, B. (2007). In silico pharmacology for drug discovery: methods for virtual ligand screening and profiling. British Journal of Pharmacology, 152(1), 9-20.

3. Franks, T. (2018). In vitro models for drug discovery. Methods in Molecular Biology (Clifton, N.J.), 1683, 11-31.

4. Pfizer. (2019). The Journey of a Medicine: From Testing to Access. Pfizer. https://www.pfizer.com/research/rd-pipeline