Cart 
EN CAR-T cell
CAR-T cell Overview
Immunotherapy is currently one of the most groundbreaking areas of cancer treatment. This advanced treatment uses your immune cells to attack cancer cells in your body. Due to T cells are good at fighting infection, but it can be difficult for them to tell the difference between a cancer cell and a normal cell. So the cancer cells can hide away and not be recognised. so, scientists are trying to find ways to get T cells to recognise cancer cells, one possible way to do this might be CAR-T cell therapy. That treatment is a type of engineered cell therapy called chimeric antigen receptor (CAR) T cell therapy.CAR-T cell therapy is a type of treatment in which a patient’s T cells (a type of immune cell) are changed in the laboratory so they will bind to cancer cells and kill them. Blood from a vein in the patient’s arm flows through a tube to an apheresis machine , which removes the white blood cells, including the T cells, and sends the rest of the blood back to the patient. Then, the gene for a special receptor called a chimeric antigen receptor (CAR) is inserted into the T cells in the laboratory. Millions of the CAR-T cells are grown in the laboratory and then given to the patient by infusion. The CAR-T cells are able to bind to an antigen on the cancer cells and kill them.
CAR-T cell working process
CAR-T cell therapy is a complex, multi-step process for patients:Apheresis:
After a patient is evaluated and determined to be a candidate for the therapy by Medical Center, treatment begins with a collection of the patient’s white blood cells, or T cells.
● Evaluation: Patients undergo a series of tests and screenings to determine if CAR-T cell therapy is an appropriate treatment option.
● Collection: T cells are collected from patients via apheresis, a process that withdraws blood from the body, and moves through a cell separator to collect the needed blood components, in this case T cells. The remaining blood components are then returned into the body.
Reprogrammed & Multiplied:
Once collected, the T cells are sent to a laboratory where they are modified with the chimeric antigen receptor protein that allows them to recognize the cancer tumor cells. The modified cells then go through a manufacturing process that can take a few weeks.
● Engineering: The T cells are sent to a laboratory where they are genetically engineered to target a specific type of cancer.
● Multiplication: The genetically modified T cells are "expanded" by growing cells in the laboratory until there are millions of them. The process of engineering and growing sufficient quantities of CAR-T cells can take a few weeks. When there are enough of them, the CAR-T cells are frozen and sent to the hospital or center where the patient is being treated.
● Conditioning Therapy: Prior to infusion of the CAR-T cells, patients may receive chemotherapy for their cancer. This helps to create space in your immune system for the infused CAR-T cells to expand and proliferate.
Infusion: After millions of the CAR-T cells are manufactured, they are frozen and sent to Medical Center where they are infused back into the patient’s blood stream.
●Infused: When the CAR-T cells are ready, the cells are infused through a central line, in a process similar to a blood transfusion. Patients may receive medications to prevent and control possible side effects of the newly-engineered cells. Patients may receive their CAR-T cells in the hospital or in the outpatient clinic. The patient's physician will decide which approach is best.
Cancer Cell Death: CAR-T cells then track down and kill the cancer tumor cells in the patient’s body.
● Recovery: Patients who receive CAR-T cell therapy have a risk/recovery period of approximately 2 to 3 months. During this period, patients will be evaluated for side effects and treatment response. It is not uncommon for patients to be admitted to the hospital during this period to manage complications from treatment. During the first 30 days after CAR-T cell infusion, patients need to remain for regular follow-up care. Throughout the entire process, careful measures are in place to ensure patients' safety.
Side effects of CAR-T cell therapy
The most common side effects seen are:● Cytokine Storm release syndrome : which is similar to flu-like symptoms (headache; fever; chills; severe nausea, vomiting, diarrhea; severe muscle or joint pain), shortness of breath, low blood pressure and fast heart rate. These symptoms are mild in most patients but can be serious and life threatening.
● Neurologic events : It may also be experienced and can be serious in some patients. Neurologic events include encephalopathy (brain disease, injury, malfunction), confusion, aphasia (difficulty understand or speaking), drowsiness, agitation, seizures, loss of balance and altered consciousness.
● Low white blood cell count (neutropenia)● Low red blood cell count (Anemia)
Fortunately, most of the side effects can be managed with drugs or resolved on their own without the need for more advance treatment.
Cytokine Storm
A severe immune reaction in which the body releases too many cytokines into the blood too quickly. Cytokines play an important role in normal immune responses, but having a large amount of them released in the body all at once can be harmful. A cytokine storm can occur as a result of an infection, autoimmune condition, or other disease. It may also occur after treatment with some types of immunotherapy. Signs and symptoms include high fever, inflammation (redness and swelling), and severe fatigue and nausea. Sometimes, a cytokine storm may be severe or life threatening and lead to multiple organ failure. Also called hypercytokinemia.
Next Generation of CAR-T cell
CAR-T cell has offered patients months or years of life after they had exhausted all other treatment options and would have died within weeks. But CAR-T cell still does have hefty limitations. potential solutions to these problems are still in the early stages, but what the future of CAR-T cell therapy might look like? It could involve synthetic biology to engineer a more advanced cell, or engineering other parts of the T cell to make it work better in the challenging environment around a tumor.● The controllable CAR-T
Current CAR-T cells use their chimeric antigen receptor, to identify and kill cancer cells. These are synthetic proteins that bind to a specific target, like a protein on a cell surface membrane, and then activate the T cell to kill any cell carrying this target. Armed with a CAR-T cells become pros at killing cancer cells that have their target, but they’ll also kill normal cells that happen to carry the protein, too. Once a CAR-T cell is in the body, there isn’t much a solution can do to rein it in if it starts causing a lot of toxicity. Researchers are trying to create CAR-T cells that they can activate or deactivate. In theory, clinicians should be able to activate a switch on the genetic circuit that induces the CAR-T cell to activate their CAR and express it on the T cell’s surface membrane, thereby activating the receptor. Then, after a while, the T cell will disarm.
There are several ways that synthetic biologists are doing this CAR with a protein switch that activates the receptor in the presence of blue light and added a gene to CAR-T cells that force it to create its CAR and express it on the cell surface, thereby activating it, only in the presence of ultrasound radiation. The idea is that the clinician can focus the light or ultrasound onto the tumor to get CAR-T cells to begin killing there. Once that signal is turned off, the CARs should disarm or slowly degrade and deactivate the CAR-T cell’s killing function. This way, even if the CAR does kill healthy tissue, the damage will theoretically be limited to the area around the tumor.● The logic-gated CAR-T
In this sense, to design the CAR-T is making a logical decision like basic Boolean computing, and synthetic biologists call this technique logic-gating.There’s a lot of cool genetic circuits can be built for conditional systems to obliterate cancer cells. It can be built OR, AND, and NOT-gates, and layer them on top of one another.
● The armored CAR-TAnother issue with conventional CAR-T therapy is that after a while, T cells can simply stop working. Solid tumors, like lung or pancreatic cancer, often have strategies to defend themselves from immune system attacks, including those from CAR-T cells. One solution si to work on “armoring” the CAR-T cell against the hostile signals in the microenvironment around a solid tumor. One of these signals is called TGF-β a protein which can help shut down T cell activity and help cancer cells avoid death and detection from the immune system. To create a CAR-T cell that is not only resistant to TGF-β, but can actually subvert the signal and become more deadly when it encounters TGF-β.
● New Cell CAR-T
Some future approaches might see new cell type . Scientists are slapping synthetic receptors on new or different cell types, such as natural killer cells or putting CARs on a synthetic cell called a CIK cell, or cytokine-induced killer cell, or creates the possibility of controlling T-cells inside the body with brief pulses of heat delivered by focused ultrasound, magnetic hyperthermia and infrared light.