Lentiviral vectors: the secret behind the rise of CAR-T therapies
CAR-T has become a hype within the biotech field recently. Companies promising to deliver this new generation of therapies are shining on stock markets, sometimes leading to billion-dollar valuations. But the rise of CAR-Ts would not have been possible without a crucial technology: the lentiviral vector!
So, what is a CAR-T again?
If you have been living in a cave (without a connection to Labiotech.eu) during the last few months, you may not know what a CAR-T therapy is. Let me explain!
Since your body is an extraordinary machine, most of the time T-cells from your immune system can identify and kill naturally occurring cancer cells. But cancer cells are robust and can develop strategies to evade or deceive the immune system, making your T-cells ineffective and therefore leading to the development of a tumor.
To enhance the ability of the immune system to identify cancer cells, engineered Chimeric Antigen Receptors (CAR) can be expressed on the surface of the T-cells, providing them with a specific cancer targeting mechanism. CAR + T-Cell = CAR-T! Your own body therefore becomes part of the treatment against the cancer!
To make this happen, a process has been developed by several Biotech companies. The first step consists of harvesting the T-cells from the patient (autologous therapy) or from a healthy person (allogeneic therapy). Then, we can transfect these cells via a vector to give them a new sequence of DNA which codes for the new receptor CAR.
Once back in the body, the engineered T-cells will express the receptors on their surface, duplicate and then flow through your body to detect and attack the cancer cells. Another advantage of this therapy is the long-term effects due to the ‘memory’ of your immune system.
Ok I get it, but what about these vectors you mentioned?
To engineer the T-cells, scientists need to go inside the cell to genetically modify its DNA genome. This is a key step, because T-cells are very refractory to the entry of foreign DNA, consequently scientists need a very efficient gene transfer tool. Currently, the most efficient way to go inside T-cells is the use of Lentiviral Vectors.
Lentiviruses are a subclass of Retroviruses. These viruses are made of an envelope, a capsid and, inside, a RNA genome. As Mother Nature works so well, the lentiviruses enter in their target cells with a very high efficiency. Once inside the cell, RNA genome is reverse-transcribed in DNA and is integrated into the genome of the cell thanks to the viral integrase enzyme. The idea is to utilize these interesting natural biological properties to serve as an efficient gene transfer tool. To this end, the genes required for the viral replication and inducing pathogenic effects are replaced by genes of interest, for example CAR! In this way, you have at your disposal a powerful vehicle to deliver your favorite CAR. Your T-cells are now supercharged against cancer!
Wait, who is producing these lentiviral vectors?
Transforming a virus into a safe and efficient vector is a long process requiring lots of specialist expertise. Finding a quality vector that will work in your experiment can be tricky, so choosing a good vector provider is a critical step for most of the laboratories working on CAR-T.
GEG-Tech is one of these providers. The French company has developed Lenti-ONETM products; a collection of Lentiviral vectors that can be used for CAR-T production.
The nature of GEG-Tech is that its high expertise in Lentiviral Vector allows it to make a real lentivirus toolkit. The GEG-Scientists appear much like the “Geeks” of the lentiviral vector technology, playing with the different features of the vector to generate different tools. For example, they mutated the viral integrase to obtain different mutants which are non-integrating, or they blocked the reverse transcription step to obtain a lentiviral vector entirely RNA. They also played with the virus’ envelope to widen the type of cell target or to restrict it to specific cells.
For a better understanding of the lentivirus toolkit and the different processes opened up by it, GEG-Tech delivers comprehensive videos but also knowledge and protocols on their website. You can also directly choose your vector of interest from their broad online catalogue (3.000+ vectors) or even customize your vector on their online platform before ordering it with, if you need, the help of their experts in vector design and project feasibility.
Is everything now clear about CAR-T therapy? I hope this brief explanation will give you a better overview of this disruptive technology. After the emergence of the monoclonal antibodies in oncology, the next wave of drugs to reach the market will certainly be using CAR-T. Stay tuned on Labiotech.eu to know everything about it!