Biologics (Cell Therapies. gene Therapy) Flashcards Preview

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Flashcards in Biologics (Cell Therapies. gene Therapy) Deck (29):

What are biological therapies?

-Peptides / recombinant therapies
- Gene therapy
- Cell therapy
- Monoclonal antibodies


What is gene therapy?

The transfer of genetic sequences that alter the DNA of a cell for therapeutic purposes

Delivery of genetic sequences that alter the instruction set of a cell for therapeutic purposes


What are the genetic sequences used in gene therapy?

- Synthetic copies of genes that encode a specific protein
- Short genetic sequences that knockdown the expression of a specific gene


Whats a variation of gene therapy?

Somatic cell gene therapy


What is somatic cell gene therapy?

Therapy is restricted to the patient and genetic material is not passed onto their offspring


What would the ideal gene therapy approach be?

- Be highly specific leading to reduced side effects
- Produce a long term therapeutic effect following a single application


What would ideal gene therapy involve?

Aim: To deliver the therapeutic gene to the organ/cell of interest

Problem: Mammalian cells are very efficient at getting rid of foreign DNA

Solution: Therapeutic genes are delivered using gene delivery vehicles


What are the gene delivery vehicles?

- Non-viral vectors : PLasmids, siRNA, lipsomes

- Viral vectors: Genetically modified viruses


How are viruses used as vectors?

- Exploit the natural life cycle of a virus
- Viruses bind to membrane bound receptors and have evolved efficient ways to gain access to the nuclear transcriptional machinery

- Remove the virus replication genetic material, left with shell, replace with therapeutic transgene
- most viral vectors nowadays are safe


How do viral vectors work?

-Penetrate a cell, use its nuclear machinery and produce therapeutic proteins(no viral genes replicated)


Whats the difference between ex-vivo and in-vivo gene therapy?

Ex-vivo = Genetic modification performed on cells in a dish before transplantation in the patient

In-vivo = Genetic modification performed directly in the patient


What does the success of gene therapy depend on?

Success of gene therapy depends on the efficiency of gene transfer


Whats the example for gene therapy?

Parkinsons disease


What does PD primarily affect?

Loss of dopamine cells in SNpc


Whats the stage one strategy for pd?

Dopamine replacement


How does dopamine replacement work?

Aim: Increase dopamine synthesis locally in the striatum

How: Transfer genes involved in dopamine synthesis to the neurons in the striatum

Problems: Does not prevent disease progression; amount of dopamine produced is hard to control


What is the second strategy for PD?



How does neuroprotection work for PD?

Aim: Boost production of growth factors involved that promote dopamine cell survival and axonal regeneration i.e glial cell derived neutrotrophic factor (GDNF) and Neurturin

How: Introduce GDNF or Neurturin genes into the brain


What is cell therapies?

Therapies involving the injection of living cells into a patient i.e bone marrow transplants


What are the types of cell therapies?

Autologous : Cells removed from patient, modified and returned

Allogenic : Cell donor is different person

Syngeneic : Cell donor is genetically identicle (twins)


What sorts of cells are used in cell therapy?

Cells can vary:

- Stem cells (cultivated into other cells)
- Blastocyte
- heDSC
- adult CNS
- Fetal CNS
- Bone marrow
- Fibroblast


How do cell therapies work?

- Replace damaged tissue
- Release therapeutic proteins


How does the replaced damaged tissues cell therapy work?

-Stem cells or progenitor cells are differentiated into a specific cell type in the lab. Cells are grafted into site of injury


How does the release therapeutic proteins cell therapy work?

- Transport cells that have the capacity to release soluble factors i.e cytokines, chemokines, growth factors

e.g insulin


What are antibodies?

Antibodies (immunoglobulins) are proteins that fucntion to identify and neutralize pathogens such as viruses or bacteria

Antibodies recognize and bind to specific antigens


What does monoclonal antibodies for human therapies involve?

- Specific for one antigen
- Typically iGg subtype
- Have been humanized or are chimeric antibodies
- Currently, commerical antibody therapies are mainly for cancer and immune disorders


What are the modes of action for many cancer immunotherapies?

- Antibody binds to a soluble ligand involved in cancer growth

- Antibody binds to a cell surface receptor on a tumor cell

- Antibody binds to tumor antigen induces human immune effector responses


What happens when Antibody binds to a soluble ligand involved in cancer growth?

- Interferes with its activity and interaction with binding partners

i.e avastin (Bevacizumab) used for treating colorectal cancer, binds to the ligand VEGF-A


What happens when Antibody binds to a cell surface receptor on a tumor cell?

- Blocks its interaction with a ligand
- Interferes with signalling pathways important in maintaining tumor growth
- triggers receptor internalisation or apoptosis of tumor cells

i.e trastuzumab (herceptin) used for treating metastatic breast cancer targets HER2 receptor