lecture 11 - cell-based therapies Flashcards
How can cell-based protein delivery be used as a therapeutic?
The proteins are encapsulated within a membrane that protects them from the immune system, so they are not rejected.
Can be used to treat diabetes - insulin-producing cells
Used to treat AD - muscle cells engineered to secrete high levels of anti-amyloid beta antibodies - these bind to plaques and enhances phagocytosis by microglial cells
How can gene therapy/genetic engineering be used as a therapeutic (cell-based delivery)?
A treatment or missing gene is added to a harmless retrovirus, which introduces it to the isolated stem cells
Or, can be delivered directly to the patient via injection
If the cells are taken from the body, we can select the cells that have actually been modified and grow them up, then insert them back into the patient
How can Strimvelis be used as a gene therapy stem cell treatment?
It is used to treat a non-functioning immune system
Isolate CD34 positive cells from the body and transfect them with the functioning copy of the missing gene
They are incubated with a retrovirus to deliver the gene and incorporate it permanently into the genome
However, one patient developed leukaemia from this treatment - the viruses inject the gene randomly into the genome, so if inserted into a TSG or oncogene, this could occur
How can engineered HSCs be used to treat sickle cell disease?
Sickle cell disease is caused by a SNP in the beta-globin gene
Autologous HSCs can be transfected with antisickling beta-globin gene
This repopulates patient’s haematopoietic space with cells which make corrected RBCs
15 months after treatment, the level of therapeutic antisickling beta-globin remained high, without the recurrence of sickle crises
How can engineered HSCs be used in HIV treatment?
HIV binds to CD4 T-cells - it needs CD4 and CCR5 to get into the cell
A patient was given a mutant CCR5, so their cells had no normal CCR5 on the surfaces
Their immune system was reprogrammed to produce stem cells that don’t have CCR5, so the HIV could not bind and infect the cells
How can immunotherapy be used to treat cancer (Tc cells, APCs)?
Cytotoxic T cells are activated by APCs (e.g. dendritic cells), which prime them with specific antigens for target cells
Tc cells then recognise and kill cells which express these antigens via release of perforin and granzyme, which induce apoptosis
This process can be improved by using cell engineering approaches - immune system can be trained to recognise cancer cells more effectively
Artificial APCs - we can isolate the RNA from the cells and convert it to DNA - use PCR to create a CDNA library specific to the cancer cells
Convert this back to RNA and load it back into the immature dendritic cells
They will produce the necessary proteins that will be expressed on the surface - these tumour-specific proteins will then train the T-cells within the patient to recognise the specific tumour that the patient has
How can CAR T-cells be used as a therapy?
These are T-cells engineered to express a chimeric antigen receptor - these proliferate and kill tumour cells upon contact with the antigen they recognise
Treats adults with certain types of large B-cell lymphoma
How can iPSCs be used as vaccines to treat cancer?
iPSCs express a number of tumour-associated antigens
Vaccination with irradiated iPSCs + CpG lead to tumour regression
Autologous iPSCs could act as personalised cancer vaccines - advantage over current immunotherapy strategies
How can PSCs be used to treat Parkinson’s?
PSCs can be differentiated into midbrain dopaminergic neurons to replace those lost in PD
Directed differentiation of PSCs can be achieved by replicating these signalling/contact conditions
How can bacteria be used as therapeutic agents?
Oxygen-deficient (hypoxic) areas of tumours tend to be chemo- and radiotherapy resistant
Many bacteria are obligate anaerobes - we can engineer them to secrete anticancer agents and can colonise hypoxic areas of tumours
We can kill them selectively with antibiotics when we no longer want them to be active
