CAR T Cells: Definition, Therapy, And Manufacturing Process

CAR T Cells Definition

CAR T-cell therapy is a type of cancer treatment that involves modifying a patient’s T cells in the laboratory to attack cancer cells. CAR T cells are genetically engineered immune cells that can recognize and target specific cancer cells.

What are CAR T Cells?

CAR T cell therapy is a type of cancer immunotherapy treatment that uses immune cells called T cells that are genetically altered in a lab to enable them to locate and destroy cancer cells more effectively.

CAR T-cell therapy is also sometimes talked about as a type of cell-based gene therapy because it involves changing the patient’s T cells in the lab by adding a gene for a receptor called a chimeric antigen receptor (CAR), which helps the T cells attach to a specific cancer cell antigen.

The process for CAR T-cell therapy can take several weeks. First, white blood cells (which include T cells) are removed from the patient’s blood using a procedure called leukapheresis.

The collected T cells are then sent to a laboratory where they are genetically modified to produce CARs on their surface. These CARs recognize and bind to specific antigens on cancer cells.

Once the CAR T-cells have been produced, they are infused back into the patient’s bloodstream, where they multiply and attack cancerous cells.

CAR-T cell therapy has been approved by the FDA since 2017 for treating certain types of blood cancers such as leukemia and lymphoma. However, this treatment is highly specialized and personalized, so it is only available at a limited number of cancer centers with specialized expertise in cellular therapies.

Natural Immune Response

The immune system is the body’s defense mechanism against harmful substances such as bacteria, viruses, and toxins. The immune response can be divided into two types: innate immunity and adaptive immunity.

Innate immunity is the first line of defense that humans are born with. It involves barriers such as skin and mucous membranes that prevent harmful materials from entering the body. Phagocytic cells are also part of innate immunity – they seek, engulf, and destroy pathogens.

Inflammation is another component of innate immunity that occurs when a pathogen invades a tissue. This response is characterized by pain, redness, heat, and swelling at the site of infection.

Adaptive immunity develops throughout our lives when we’re exposed to diseases or when we’re immunized against them with vaccines. Adaptive immunity involves lymphocytes (T cells and B cells) that recognize specific antigens on pathogens.

Once a pathogen enters the body, it is recognized by antigen-presenting cells (APCs) which present the antigen to T cells. Activated T cells then help B cells produce antibodies that specifically target the pathogen.

Adaptive immunity provides long-term protection against specific pathogens because it creates memory cells that “remember” how to fight off a particular pathogen if it enters the body again in the future.

Natural immunity refers to acquired immunity from exposure to a disease organism through infection with the actual disease. Vaccine-induced immunity is acquired through vaccination with weakened or dead forms of a pathogen or parts of a pathogen called antigens.

A study suggests that COVID-19 survivors have lasting natural immunity against reinfection with the SARS-CoV-2 virus but vaccination can provide an additional boost to their immune system.

CAR T Cells and Cancer

CAR T-cell therapy is a type of immunotherapy that uses a patient’s T cells, which are changed in the laboratory to bind to cancer cells and kill them.

The T cells are collected from the patient and re-engineered in the laboratory to produce proteins on their surface called chimeric antigen receptors (CARs). The CARs recognize and bind to specific molecules on the surface of cancer cells, improving the ability of T cells to attack cancer cells.

Currently, CAR T-cell therapies are approved for the treatment of blood cancers, including lymphomas, some forms of leukemia, and multiple myeloma. However, researchers are studying CAR T-cell therapy for other types of cancer as well.

One potential side effect of CAR T-cell therapy is cytokine release syndrome (CRS), which occurs when the immune system responds aggressively to infused CAR T-cells. CRS can cause fever, low blood pressure, and organ damage. However, side effects can be managed with appropriate medical care.

CAR T-cell therapy has shown promising results in clinical trials. For example, in a clinical trial involving children with acute lymphoblastic leukemia (ALL), 60% were still alive 5 years later without their cancer coming back or experiencing any disease-related problems.

What is CAR T Cell Therapy?

CAR T-cell therapy is a type of cancer immunotherapy that uses immune cells called T cells to fight cancer by adding a gene for a receptor (called a chimeric antigen receptor or CAR) that helps the T cells attach to a specific cancer cell antigen.

The process for CAR T-cell therapy can take several weeks. First, white blood cells (which include T cells) are removed from the patient’s blood using a procedure called leukapheresis. During this procedure, patients usually lie in bed or sit in a reclining chair.

Two IV lines are needed because blood is removed through one line, the white blood cells are separated out, and then the rest of the blood is returned through another line. Once enough CAR T cells have been made, they will be given back to the patient.

CAR T-cell therapy has proven very effective at treating acute lymphoblastic leukemia (ALL) in both children and adults. It is also being studied in the treatment of other types of cancer such as lymphoma, lung cancer, breast cancer, mesothelioma, ovarian cancer, and multiple myeloma.

Because this is a highly specialized and personalized treatment, CAR T-cell therapy is available at a limited number of cancer centers with specialized expertise in cellular therapies such as Dana-Farber Brigham Cancer Center and Dana-Farber Boston Children’s Cancer and Blood Disorders Center.

CAR T Cells Manufacturing Process

CAR T cell therapy is a type of immunotherapy used to fight cancer with a patient’s own altered immune cells. The process of manufacturing CAR T cells begins with the collection of mononuclear cells (MNCs) from the patient’s blood via leukapheresis.

CD3+ T cells may be further enriched ex vivo and then modified to express a transgene encoding a tumor-specific CAR. The CAR-coding viral DNA is incorporated into the T cells through reprogramming.

The T cells are activated using artificial antigen-presenting cells (aAPCs), transduced with the CAR-encoding viral vector, and expanded to large numbers in a bioreactor.

Traditional manufacturing approaches require T cells to be stimulated in a way that induces the cells to replicate and expand in number, which can take several weeks. However, researchers at Penn Medicine have developed a faster engineering time that can shorten the manufacturing time for CAR T cells.

This approach involves using messenger RNA (mRNA) instead of viral vectors to deliver genetic instructions into the T cells. This method allows for rapid gene expression without integrating into the genome, which reduces the risk of off-target effects and shortens manufacturing time from weeks to days.

CAR T cell therapy has shown promising results in clinical trials, but there are still challenges associated with its use. One challenge is ensuring that enough high-quality CAR T cells are produced for each patient.

Researchers are exploring ways to automate and streamline the manufacturing process while maintaining quality control standards. Another challenge is managing side effects such as cytokine release syndrome (CRS) and neurotoxicity. Researchers are developing strategies to mitigate these side effects while maintaining therapeutic efficacy.