Formulation of Biotech Products

Learning Objectives

• Describe the use of antibodies for targeted delivery systems.

• Explain Antibody Drug Conjugates (ADCs) and their different components.

• Compare the mechanism of action of virus-based and mRNA-based vaccines.

Application of Antibodies as Targeting Agents

• Strategy I: Conjugate drug with monoclonal antibodies (MAb).

• Strategy II: Conjugate drug delivery systems (liposomes, nanoparticles, polymers, etc.) with MAb.

• Antibodies have high specificity for antigens expressed on targeted cells, such as liver and tumor cells.

• Target cells are specifically killed while sparing normal cells.

Antibody Drug Conjugate (ADC) Overview

• ADCs consist of a monoclonal antibody linked to a cytotoxic antitumor drug.

• As of now, 15 ADCs have been approved by the FDA.

• The first-ever approved ADC, Mylotarg, was withdrawn in 2010 due to ineffectiveness and severe side effects in post-approval trials.

• There are more than 359 ADCs currently in clinical trials.

Components of an Antibody Drug Conjugate (ADC)

1. Antibody: Specific for a tumor-associated antigen with limited expression on normal cells.

2. Linker: Designed for stability in circulation and to release the cytotoxic agent inside the target cells.

3. Cytotoxic Agent: Formulated to kill target cells upon internalization and release.

   • References for further reading include studies and papers on ADCs published in cancer journals.

Case Study: Trastuzumab Emtansine (T-DM1)

• A derivative of maytansine combined with trastuzumab.

• Employs antibody-dependent cellular cytotoxicity (ADCC) targeting HER2 expressed in breast cancer.

Immunoliposomes for Targeting HER-2

• Immunoliposome: Spherical vesicles with a lipid bilayer membrane, conjugated with single-chain variable fragment (scFv) targeting HER-2.

• Anti-tumor drugs are encapsulated in liposomes, showing specific binding and killing of breast tumor cells.

• Capable of encapsulating multiple drug molecules.

Targeted Drug Delivery

• Immunoliposomes provide enhanced binding to targeted cells due to specific receptors, increasing efficacy compared to non-target cells.

Comparison of COVID-19 Vaccines

• Storage Conditions:

  • Pfizer: mRNA vaccine stored at -70 °C.

  • Moderna: mRNA vaccine stored at -20 °C.

  • Oxford-AstraZeneca: Weakened virus stored at 2 to 8 °C.

Mechanism of Action of mRNA Vaccines

• mRNA vaccines prompt cells to produce viral proteins that stimulate a strong immune response.

• The vaccine sequence consists of mRNA coding for the spike protein, enveloped in lipid for delivery.

• Healthy cells generate antibodies to protect against actual virus infections.

Mechanism of Action of Oxford-AstraZeneca Vaccine

• Utilizes a modified harmless chimpanzee adenovirus as a vector to deliver the spike protein gene from the coronavirus.

• Triggers an immune response to generate antibodies, preparing the body to combat the actual viral infection.

References

• Ansel's Pharmaceutical Dosage Forms and Drug Delivery Systems, 12th Edition, Loyd V. Allen Jr. and Timothy B. McPherson (2021).

• Khan et al. (2022). In: Khan, S.A. Essentials of Industrial Pharmacy. Springer, Cham.

• AULTON, M. E., TAYLOR, K. (2013). Aulton's Pharmaceutics: the design and manufacture of medicines, Edinburgh, Churchill Livingstone.