How scientists are using engineered cells to defeat disease
Cell-engineering is creating a new generation of therapies to target intractable diseases, including cancer Image: REUTERS/Chaiwat Subprasom
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Biotechnology
Today’s drugs generally consist of a single active molecule that once administered functions by interacting with disease-related pathways to impart a clinical benefit.
Given the complexity of our biology, this is a relatively simplistic approach to disease treatment which can have limited efficacy and result in side effects.
Now we are seeing the emergence of a new class of drugs where a living cell is modified and used as a therapeutic.
The active molecule of most drugs cannot discriminate between the diseased parts of our body and the healthy parts, resulting in unwanted side effects that can sometimes be severe enough to cause new diseases or even death. Treating cancer with chemotherapy, for example, is a balancing act of using drugs to kill all the cancerous cells before the drugs kill the patient.
Incredible immune system
Compared to such blunt, non-specific drugs, our immune system is a complex, highly effective system, responsible for protecting us against most diseases and keeping us healthy for the duration of our lives.
The immune system consists of a wide variety of cell types that function in unison to combat disease. Some immune cells sound the alarm when a problem is suspected, and other cells can detect unique disease features that can stimulate killer cell activity or an antibody response.
The immune system can also form long-lasting memories specific to the disease for faster response times should the disease re-emerge. Despite its incredible capabilities, the immune-system cannot combat some diseases unaided.
Working with natural defences
This contrast in effectiveness and specificity of pharmaceuticals versus natural biological defences has inspired many scientists to work with the immune system, which has evolved to work in such a beautifully precise way.
With this approach, scientists can develop cell-based therapies that use engineered cells from the immune system as the “drug”.
Properly engineered immune cells could enable scientists to direct highly specific, long-lasting immune response mechanisms against a disease.
In contrast to individual molecules, which are more limited in their capabilities, cell-based therapies would be capable of deploying the full spectrum of natural defence mechanisms to combat the disease.
Detect and destroy
One recent advance in cell-based therapies is the dramatic progress of chimeric antigen receptor T (CAR-T) cell therapies in the treatment of certain blood cancers. CAR-T cells are human killer T cells artificially engineered to target specific proteins (antigens) associated with a cancer.
Using this artificial targeting system as a guide, CAR-T cells can detect and destroy cancer cells very effectively.
Clinical trials in some blood cancers have shown that for patients where multiple rounds of traditional chemotherapeutics have failed, these engineered killer CAR-T cells are a potential cure.
Initial successes, such as CAR-T cells, indicate that there is enormous potential for cell-based therapies to address currently intractable diseases.
Multiple challenges
However, progress in the field of cell engineering to date has been limited by many challenges.
One such challenge is the ability to successfully deliver into cells the molecular components necessary to alter cell function.
Individual cells have multiple barriers that protect the cell from manipulation, including the cell membrane and myriad internal enzymes. Hence, development of technologies capable of effectively overcoming these barriers for delivery of cell engineering materials, while preserving critical cell functions, is vital to success.
SQZ Biotech, for example, has developed a platform capable of delivering almost any material of interest into a wide range of cell types.
This microfluidic platform has enabled modulation of cell functions that were previously inaccessible.
New generation of therapies
The SQZ approach minimizes effects on normal cell function and viability, thus dramatically expanding our ability to engineer cells.
With these technological advancements, scientists can generate a whole new generation of therapies to address diseases, including cancer, autoimmune disorders, and infectious diseases that have thus far proven extremely difficult to treat.
This evolution towards cell-based therapies marks a significant development in our approach to disease treatment, leveraging the power of a patient’s own sophisticated defence mechanisms to better combat disease.
As we see more cell therapies entering clinical trials, we can expect to see some truly exciting improvements in outcomes for patients.
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