Our bodies are continuously targeted by pathogens that view us as a vulnerable fortress to infiltrate. Fortunately, you have a security team in the form of your immune system, with white blood cells serving as your primary soldiers to battle these invaders. They check protein fragments on the surface of cells called antigens. There are two types of WBCs, namely T cells and B cells.
T cells have receptors that latch onto these antigens and if they find a match they burst open the invading cell’s membrane by releasing toxins.
B cells create antibodies that attach to these cells, marking them for destruction.
WBCs are efficient at spotting pathogens that invade from the outside. However, they struggle to recognize one's own cells that have turned rogue. The antigens on cancer cells don’t look foreign, they look identical to your own cells and WBCs aren’t programmed to recognize them.
Conventional methods of treating cancer - by cutting out the tumor or using radiotherapy followed by chemotherapy are futile when it comes to treating blood cancers, especially if they start in your WBCs.
That’s the case with acute lymphoblastic leukemia. Here, a bio-hack like (Chimeric Antigen Receptor) CAR T Cell Therapy becomes vital for survival.
The name comes from a fire breathing monster from Ancient Greece - that had a lion’s head, a goat’s body and a serpent’s tail. ‘Chimera’ - a name that has now come to be used for something that contains two or more different types of tissues or cells.
It involves reprogramming a patient’s own immune system to recognize particular antigens on a cancer cell.
Millions of T cells from a patient are harvested. Synthetic biologists employ a computer to assemble a custom sequence of genetic bases, simulating the effects of this new genetic code on a computer before fabricating those sequences on the T cells using a DNA printer.
The newly engineered T cell features three pivotal directives:
1. It instructs the T cell on how to identify and eliminate cancer cells, specifically by altering an antibody to create a novel receptor capable of detecting the specific antigen present on the cancer cell.
2. It guides the T cell to replicate itself upon encountering a cancer cell.
3. It ensures the T cell’s survival within the patient’s body.
To get this new code into the patient’s T cells, a vector is used - it is something that will easily infect the T cell and carry the bespoke DNA which results in the creation of one CAR T cell.
Before the multiplied T cells are put back into the patient’s body, a mild dose of chemotherapy is given to wipe their existing T cells. Then the now modified T cells are reinserted and they follow their normal DNA programming to move and search cancer cells and destroy them. The CAR T-cell therapies approved by FDA to date, target one of two antigens on B cells, CD19 or BCMA.
Unlike chemical based conventional drugs that get used up or excreted from the body pretty quickly, CAR T cells are living drugs that stay in the patient’s bloodstream for years.
Drawbacks of this approach include its high cost - which may go up to $450,000; the necessity for patient-specific designs; and the challenge of adapting it to common cancers such as breast or lung cancer, which require specific antigens on cancer cells for CAR T cells to target.
CAR T-cell therapies, like other cancer treatments, can lead to severe side effects, notably cytokine release syndrome (CRS), where infused T cells flood the bloodstream with cytokines, causing high fevers and blood pressure drops, which can be fatal in severe cases. Tocilizumab is effective in treating CRS.
The other side effect of particular concern with CAR T-cell therapies is neurologic effects, including severe confusion, seizure-like activity, and impaired speech.
CAR T-cell therapy is typically considered when other cancer treatments fail, but it's becoming a primary option. Recent clinical trials showed its effectiveness in non-Hodgkin lymphoma patients after initial chemotherapy failure, suggesting it may replace chemotherapy as the second-line treatment for this group.
With the potential for improved long-term outcomes, reduced side effects, and expanded availability, CAR T-cell therapy stands as a beacon of hope in the ongoing battle against cancer.
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by-DARSHITA SALIAN
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