How scientists make ‘living drugs’ to defeat cancer

Examination of the patient’s tumor under a microscope shows that, even if a larger immune attack has failed, a few T-cells still try to successfully identify tumor antigens and find their way to invade. . These powerful intruders would be Mr. cells. Their Perfect T and, hopefully, the seed for clones to kill their target cancer.

Hwu’s focus is on attempting to weaponize this successful “tumor-penetrating lymphocyte” subset, or TIL, by encapsulating them with an additional dose of powerful tumor-killing hormones. . “Zelig has demonstrated that an antibody and a T cell can be combined to target something,” said Hwu, head of cancer medicine at Anderson Cancer Center in Houston, Texas. there. “Now the question is, can we make it target cancer cells?”

To act as small guided rockets, they need a navigation system, one that researchers can select and customize to target different types of cancer. It started with a bunch of T cells they found to be Mr. Perfect TILs worked against melanoma, Hwu and Eshhar Frankensteized them with new TCRs to instead target ovarian, colon and breast cancers. “Zelig makes receptors, I put it into T cells,” Hwu recalled. “It was really hard to do that in the 1990s.”

Without the benefit of the retroviral or Crispr vectors, the task entails inserting a fine needle into the T cell and microinjecting the new TCR genes into each cell. “We spent a lot of time together,” said Hwe with a laugh. “Lots of people all night in the lab.”

Neither result was perfect, but the TILs they re-targeted for ovarian cancer performed best of the three, and the team was able to publish the results, heralding the name CAR-T. new and interesting effects of technology.

They did not cure any cancer, but they made scientific progress. They have successfully replaced the T-cell steering wheel and know how to find a specific cancer. “The first time I did it, I was so excited,” Hwu recalled. But it will take more than re-targeting to design a cancer-killing machine.

To be effective, these new cells also need to grow and regenerate, just like normal T cells. Their first generation cars didn’t do that. It is as if some key essence was lost during retrofit, resulting in the CAR Lemon not running long enough to regenerate or destroy. Their Frankenstein would get up from the table, only to bow.

Researcher Michel Sadelain will depend on coming up with clever solutions to this and a number of other technical problems, creating a real “living medicine”, as Sadelain calls it, a second generation CAR. two are able to recognize the target, expand asexually and retain other T-cell functions, with a life span as long as the patient’s life.

Working in his lab, Sadelain (a laconic scientific intellectual, is the founding director of Memorial Sloan Kettering’s Cell Engineering Center, among other things) also gives his new CAR a new target. Important – a protein called CD19 is found uniquely on the surface of some blood cancer cells.

The CD-19 seems to be a good XE option. It is found a lot on the surface of some cancers. It is also expressed by some normal B cells, but that is acceptable. If CAR attacks healthy cells as well as cancer, the mortgage damage may survive.

In healthy people, B cells are essential aspects of the normal immune system. But in patients like Emily, those B cells have mutated and become cancerous. In order to survive, she needed to lose them.

Fortunately, doctors have long known how to keep patients alive without B cells. “If you’re dealing with end-stage cancer,” says Sadelain, “loss of cells. Your B is not too bad ”.

Sadelain now has a sleek, stylish and renewable second-generation XE with plenty of fuel and realistic cancer targets. His team shared their new CAR sequences with Rosenberg’s group at the National Cancer Institute, as well as researcher and doctor Carl June’s lab at the University of Pennsylvania. (June also relied on aspects of his CAR design on a sample borrowed from St. Jude Children’s Research Hospital Dario Campagna.)

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