Chimeric antigen receptor (CAR) technology

Chimeric antigen receptor (CAR) technology

Once again, a brave new world  in Oncology is upon us. Chronic Lymphocytic leukemia is the most common form of chronic leukemia in adults and although it for a period is highly treatable ,  with both chemo therapy and immunotherapy, patients ultimately succumb usually from infection and die. For decades , researchers have sought to find a target on CLL cells, not on normal lymphocytes, that engineered killer T lymphocytes  from the patient’s own body can be reengineered to attack what is not self( the leukemia) and leave the rest alone. Although the below report  below is only a handful of patients, the point is the proof of principal that “signature” therapy  can be a reality; in this case reprogramming a patient’s T cells to “hunt” and destroy cancer cells

  1. Individualized CAR T cell therapy uses the patient’s own immune system to kill cancer. Outside of a patient’s body, the patient’s own T cells are reprogrammed to express receptors on their surface that allow them to recognize a specific protein expressed by tumor cells. Once re-infused into the patient, these cells “hunt” and potentially kill tumor cells.
  2. The patient receives lymphodepleting chemotherapy to reduce the level of white blood cells and help the body accept the reprogrammed T cells
  3. White blood cells, including T cells, are separated from the patient’s blood in a process called leukapheresis. They are then sent to a manufacturing facility for reprogramming. Using an otherwise inactive  Viral vector, ( safe carrying a message piece of virus) the necessary genetic material for T cells to recognize a protein cell surface receptor on the CLL cells ( CD 19)( but not on normal cells)  is inserted into the patients’ T cells DNA

4.The reprogrammed T cells are reintroduced into the patient’s blood.

  1. Within the patient’s body, the T cells expand. The CTL019 cells “hunt” cancer cells expressing CD19, attach to them, and initiate direct cell death.

Amazing , sounds simple, was sketched out in the 1980’s as a plan and took until now to go forward as there was  lot of science to be discovered and tools to be built and converge

6. Once the gene transfer is complete, T cells are now reprogrammed to “hunt” cancer cells by expressing a CAR on its surface. For CTL019, the T cell is programmed to hunt the CD19 protein on the surface of B cells. Cancer cell death is initiated after CTL019 attaches to cancer cells

Using the body’s immune system to combat cancer is not a new approach; however, it has taken decades of research to increase our understanding of immune cells (T cells) and the signals they use to attack targets. With CAR technology, in contrast to other approaches to personalized cell therapies for the potential treatment of cancer, T cells are drawn from a patient’s blood and modified in the laboratory to create “chimeric” ( of more than one DNA source) T cells genetically coded to “hunt” and potentially kill tumor cells. When these T cells are infused back into the patient, they become a new part of the patient’s immune system specifically designed to target the patient’s cancer.

About CTL019

CTL019 is an investigational, personalized T cell therapy which was pioneered by Dr. Carl June and his team at the University of Pennsylvania (Penn). CTL019 Phase I/II trials advances Novartis’ understanding of the novel CAR personalized cell therapy.

( Dr Kevin Ryan )

Long-Term Remissions of CLL in First Personalized Cell Tx Trial

T cells reprogrammed to contain chimeric antigen receptor targeting CD19 protein on B cells

An experimental therapy for chronic lymphocytic leukemia that uses a patient’s own T cells (an approach known as CTL019) may cure some patients and prolong survival in others, researchers report. The study was published in the Sept. 2 issue of Science Translational Medicine.

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