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October 13, 2020
Recent Publication Added
Published May 2020
Locoregionally administered B7-H3-targeted CAR T cells for treatment of atypical teratoid/rhabdoid tumors
 
Publication Summary:

Immunotherapies – treatments that improve the body’s natural defenses against invaders like cancer – are a rapidly developing area of cancer treatment. But in order to work, scientists must first identify a facet of the malignancy that’s different from healthy tissue and a means to target that difference. 

A protein called B7-H3 has been found in several types of tumor tissues. It’s associated with poorer outcomes and shorter survival times, leading researchers to suspect that it might play a role in regulating the body’s response to cancer.

B7-H3 also can be found in abundance on the surface of certain cells in the developing brains of babies before birth.  Once the baby is born, B7-H3 levels decrease markedly. But in babies who are diagnosed with ATRT, B7-H3 levels remain high; almost all ATRT tumors test positive for the protein. It’s thought that B7-H3 may help ATRT cells to evade the body’s natural defenses.  

In a recently published letter to the journal Nature Medicine, researchers proposed that it might be possible to interrupt that lethal relationship through an immunotherapy approach called CAR-T. Normal immune system defenders called t-cells are gathered from a patient’s blood and reprogrammed in the laboratory to seek out and neutralize a target, in this case B7-H3. The researchers theorize that neutralizing B7-H3 would unmask ATRT cells so that the body’s normal defenses could attack them.

To test this, researchers took tissue samples of ATRT tumors removed from pediatric patients. They then injected cells from the ATRT tissue into the skulls of specially developed mice with an immune system that would allow the tissue to grow. CAR-T treatment was then administered to the mice in three different ways: intravenously, directly to the tumor tissue, or through an injection into the space where fluids normally flow between the brain and spinal cord (ICV). 

Their findings showed that intravenous CAR T took longer to reach the ATRT tumor in the brain. CAR T injected directly into the tumor or through ICV eradicated all ATRT tumors in the mice. Achieving similar results with intravenous CAR T required a much higher dosage, at levels that could cause significant side effects in humans. They also found that the CAR T cells multiplied and spread beyond the brain in these mice, which might help fight similar types of rhabdoid tumors that can occur in the kidneys.

B7-H3 is a promising target for ATRT immunotherapies. But more study will be necessary before these findings can be tried in the human setting.

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