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Manufacturing of Gene therapy and Monoclonal antibodies - Coggle Diagram
Manufacturing of Gene therapy and Monoclonal antibodies
1) Introduction
Monoclonal Antibodies
History:
First approved mAb by US FDA in
1986
OKT3 renamed muromonab-CD3
Definition:
Man made versions of immune systems proteins to aid the humans immune system to fight against the antigen
Background Information
Initially they were mouse antibodies which were valuable in laboratory and animal research but problematic as therapeutic agents
Applications
: Therapeutics, Diagnostics, Clinical
Manufacturing
Overview of Bioreactors
Cell culture:
contributes the largest component of manufacturing time and affects cell product
characteristics
Maintains culture environment
Advantages of using bioreactors (in vivo) instead of Ex vivo
reduced manufacturing costs, improved process control, improved quality and consistency
Upstream bioprocessing
: Proteins are produced by cells being genetically engineered to contain the human gene which will express the protein of interest
Expression system, fermentation, product production
Definition:
A bioreactor is a stand alone cell culture vessel enabled with sensors
Gene/cell therapy
Definition:
Involves the transfer of genetic material usually in a carrier or vector with the relevant function and uptake of the gene into the appropriate cells of the body
History
: The FDA approved Kymriah (tisagenlecleucel) first gene therapy in 2017
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Background Info:
In vivo & Ex vivo
Diseases treated by Gene therapy
Numbers of patients who have received effective gene-based therapy is few but has potential to become a game changer in modern therapeutic medicine
3) Gene/Cell therapy
About gene/cell therapy and its potential
Gene and cell products are paving the way towards more effective therapeutics for unmet medical needs
Threat complex diseases and conditions such as cancer, tissue injuries and revoluntionary vaccines
Cancer is the most common disease treated by gene therapy (60%)
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Products may be used to modify cells in vivo or transferred to cells ex vivo prior to administration to the recipient
Starting material
Patient and donor cells = highly complex
HEK cells e.g. HEK293
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Derived from human embryonic kidney cells
Heterogenous mix of cells in the body
Advantages/Difficulties using human cells
Stirred tank bioreactors versus single use bioreactors for gene therapy
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Description of Stirred tank bioreactors
Advantages & limitations
Description of single use bioreactors
Advantages & limitations
Opinion on which bioreactor is better for gene/cell therapy
Vectors
What are Vectors?
Vehicles used to introduce the transgene is known as vectors
Types of Vectors
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Viral vectors
Retrovirus
RNA virus
reverse transcription to from DNA
Retrovirus is one of the best choices for gene therapy as it can integrate DNA efficiently into the host genome
Negatives
Oncogenic activity
Uncontrolled integration
Can not infect non-dividing cells
Adverse effect
Provoke immune response
Positives
Stable integration
Infect replication cells
Suitable for ex vivo treatment
Adenovirus
Made up of double stranded DNA
Positives
Infect both dividing's as well as non dividing cells
Less chance of infection
Negative
Provoke strong immune response
Non-viral vectors
They are non toxic, non-immunogenic and tissue specific
2) Monoclonal antibodies
Chinese Hamster Ovary Cells
Definition:
Mammalian cells used to produce a desired protein of interest
CHO are the main cells used to produce biotherapeutics and account for 84% of total mAbs produced in cell
culture
Theodore Puck 1957
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Advantages:
easy to cultivate, capable of growing at high cell densities, ability to produce diverse, correctly folded and glycosylated proteins
Features for successful CHO cell culture in the bioreactor
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Slow and gentle mixing
High end gassing system
Foam prevention
Accurate feeding
Sterile sampling
Fed batch Versus Continuous bioprocessing
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What is Fed batch bioprocessing?
What is Continuous bioprocessing
Opportunities and challenges for continuous bioprocessing
4)
Manufacturing of Monoclonal Antibodies versus Gene/Cell therapy
Difficulties/Differences
between mAb and Gene/Cell therapy based on findings
Similarities
between mAb and Gene/Cell therapy based on findings
The future of manufacturing
The potential for gene/cell therapy
Single use bioporcessing