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Scientists Engineer Immune Cell to Target Wide Range of Tumors

A novel immunotherapy molecule designed in the laboratory at Stanford University School of Medicine was able to eliminate several types of pediatric cancers and has shown promise against a number of other forms of malignancy.  Childhood and brain cancers are two fields that badly need new solutions, as they are particularly difficult to treat and [...]

A novel immunotherapy molecule designed in the laboratory at Stanford University School of Medicine was able to eliminate several types of pediatric cancers and has shown promise against a number of other forms of malignancy.  Childhood and brain cancers are two fields that badly need new solutions, as they are particularly difficult to treat and often associated with poor outcomes.

The prognosis for children with relapsed brain tumors or solid tumors or metastatic disease generally is dismal”, noted Robbie Majzner, MD, lead investigator.  “We’re excited that we have a potential therapeutic representing a completely new modality to treat these children”.

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While immunotherapies have been highly successful in recent years, they are still limited in terms of targetable diseases, especially when it comes to solid tumors.  To improve their approach, the team drew inspiration from a biological therapy that uses chimeric antigen receptor (CAR) T cells and took it further.

For this method, T cells (a subtype of white blood cell that mediates immune responses) are removed from a patient’s blood, changed in a laboratory so they have specific proteins called receptors and then transfused back.  This way the body’s own defense system can seek out and destroy the cancer cells.

In order to find a suitable receptor to graft, the team screened 388 pediatric tumor samples for expression of a surface marker called B7-H3, which prior studies suggested might be a good candidate.  It was found in 84% of the specimens.  This is a common marker for many pediatric cancers, including Ewing sarcoma (bone), rhabdomyosarcoma (muscle), Wilms tumor (kidneys), neuroblastoma (nerve cells) and medulloblastoma (brain).

Researchers then developed six types of CAR-T cells to target B7-H3 and tested them against several xenograft models of pediatric cancer, in which human tumors were implanted in mice.  The procedure managed to eradicate the tumors.

The tumor just goes away”, Majzner said.  “It’s very consistent.  It happened in all the mice, and that’s exciting”.

The engineered cells were also able to tackle metastasized cancers that had spread to the lung and even cross the blood-brain barrier to attack medulloblastomas.

Treatment was observed to be well taken and safe, even though some healthy cells produce low levels of the marker B7-H3.

Clinical trials are the next step, and the team is working on optimizing the procedure in the meantime.  This could open the door for many new treatments and help countless patients suffering from cancer.

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