lec23_formulation of biotech products (III)(1)
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.
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.
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The first-ever approved ADC, Mylotarg, was withdrawn in 2010 due to ineffectiveness and severe side effects in post-approval trials.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.
Antibody: Specific for a tumor-associated antigen with limited expression on normal cells.
Linker: Designed for stability in circulation and to release the cytotoxic agent inside the target cells.
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.
A derivative of maytansine combined with trastuzumab.
Employs antibody-dependent cellular cytotoxicity (ADCC) targeting HER2 expressed in breast cancer.
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.
Immunoliposomes provide enhanced binding to targeted cells due to specific receptors, increasing efficacy compared to non-target cells.
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.
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.
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.
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.
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.
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.
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.
Antibody: Specific for a tumor-associated antigen with limited expression on normal cells.
Linker: Designed for stability in circulation and to release the cytotoxic agent inside the target cells.
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.
A derivative of maytansine combined with trastuzumab.
Employs antibody-dependent cellular cytotoxicity (ADCC) targeting HER2 expressed in breast cancer.
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.
Immunoliposomes provide enhanced binding to targeted cells due to specific receptors, increasing efficacy compared to non-target cells.
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.
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.
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.
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.