From the day you were conceived, your body has been busy dividing its cells rapidly and today you are comprised of 37 trillion cells of different form and function. With 3 billion nucleotide bases to copy for each division cycle, your DNA can aggregate nearly a trillion mutations every time the cell divides.
Luckily, our cells have advance mechanisms that allow proof reading of the DNA. However, with enough mutations, the cell can override the standard set of times it must multiply. It could then potentially escape ‘apoptosis’ and recklessly divide forming a cancerous cell.
Since the 1960’s, chemotherapy and radiation are known to be the most successful and widely used techniques for the treatment of cancer. Here we discuss a relatively new method, CAR T-Cell Therapy.
CAR T-Cell Therapy – Explained
The first generation of CAR-T cells was developed by Zelig Eshhar in 1993. Today it is used to treat leukemia in children and young adults. To understand what CAR-T cells do, we first need to look into how the immune system functions, and specifically what T cells do.
Lymphocytes or white blood cells play a crucial role in fighting infection and diseases, including cancer. T cells are one type of lymphocytes. T cells circulate in the blood stream, patrolling for any infection or defective cells which need to be destroyed. When they identify a new infection or disease, your body will make T cells fight that specific infection or disease. It will also store a reserve of T cells so if you come across the same infection again, you body will already be able to recognize it and fight easily.
T cells are very efficient in fighting the infection that an invaded into our bloodstream. However, they are poor in identifying the difference between a normal cell and cancerous cell. This is because the cancerous cell and the normal cell exhibit similar MHC proteins. Thus, cancer cells are able to hide in plain sight. But what if there was a way to arm the T cell with additional proteins receptors that can identify the cancerous cells and attacking it with an overwhelming army. Scientists are trying to find ways to get T cells to recognize cancer cells. One possible way to do this might be CAR T-cell therapy.
When the cells are bought in the lab, different immune cell parts are assembled using genetic editing. This is simliar to the chimera in Greek mythology (an animal which was the combination of goat, lion and serpent) and hence the name ‘Chimeric Antigen Receptor T cell” or simply CAR T-cell.
Genomic editing techniques such as CRISPR have allowed CAR T-cell therapy to become a reality. Though this engineering can be complex, the concept is simple. Each individual T cell has a receptor known as a T cell receptor (TCR) which is able to identify a distinct ‘sick’ cell. This is how T cells ‘see’. If you change the TCR, you can change what the T cell ‘sees’. It’s similar to providing T cells with addition night vision googles and now they can easily spot the cancer cells hiding in the dark. The target chosen is CD-19, a molecule abundantly present in cancerous cells.
And these cells can expand clonally and thrive in the body, all while retaining its genetically engineered functionality. A single CAR T-cell can take on hundreds of cancerous cells, which is why this ‘living drug’ is also known as ‘serial killers’. This therapy has been extremely effective in ‘liquid’ cancers such as leukemia.
Developed in 1975 by Georges Köhler and César Milstein, this is one of the smartest and most effective way the immune system can be tuned to fight cancer. They even shared Nobel Prize in Physiology or Medicine in 1984 for its development.
Cancer cells are conniving, they can very well disguise themselves as normal cells. Thus, they are able to easily hide from the T cells that patrol the blood stream. Cancer cells also present check point protein PD-1. This is commonly associated with normal cells. T cells do not attack the cells which present this protein on their surface.
This is where monoclonal antibodies help out. They are able to block these checkpoint proteins on the cancer cells. By attaching to the surface, monoclonal antibodies tag the cancerous cells. This catches the T cells attention and then T cells are able to destroy the cancerous cell.
Scientists are working on conjugated monoclonal antibodies that carry a drug (chemotherapy drug or radioactive molecule). When the monoclonal antibodies identify a cancerous cell, they not only tag the cell, but also deliver the drug. This allows the cancer to slow down while the immune system is activates itself.(Reference)
The Success Story of Herceptin
Most cancer cells overwork and produce excessive proteins resulting in rapid growth and division. A good example of this is HER2 protein. It is mostly the case in breast and ovarian cancers.
Herceptin’s structure allows it bind to HER2 protein and slow the cancer.