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Engineered T-Cells Tested on Metastatic Cancer

KRAS protein structure

KRAS protein structure illustration (National Cancer Institute)

12 December 2016. An individual with lung cancer tumors that spread from the colon had the tumors reduced in size after a single treatment of modified cancer-killing immune system cells. A report of this case, using a technology developed by biotechnology company Kite Pharma Inc., appears in the 8 December issue of New England Journal of Medicine (paid subscription required).

Kite Pharma, in Santa Monica, California, develops personalized cancer therapies based on the patient’s own T-cells, white blood cells that the immune system uses to fight invading pathogens. The company, founded in 2009 by UCLA urologist and cancer specialist Arie Belldegrun, is based on a technology that alters a patient’s T-cells to attack the the cancer. Belldegrun is now Kite’s CEO and board chair.

In Kite’s technology, T cells are genetically engineered to produce special receptors on their surface that attract an antigen fighting the cancer. The engineered T cells are then grown in the lab in large quantities and infused back into the patient, where they attract the antigen proteins and fight the cancer. In cases like the one reported in the article, the receptors attract and bind to neoantigens, those not encountered previously by the immune system.

Kite Pharma’s technology in this case modifies T-cells to attack tumor cells expressing a mutation known as G12D of the KRAS gene. The KRAS oncogene, genes where mutations are closely linked with cancer, is believed responsible for 95 percent of pancreatic cancers and nearly half (45%) of colorectal cancers.The G12D mutation is the most common for the KRAS gene and implicated in some 50,000 new cancer cases each year in the U.S.

Kite Pharma licensed the technology in September 2016 from National Cancer Institute or NCI, part of National Institutes of Health, that conducted the original research. Under the agreement, NCI was paid an initial licensing fee by Kite, and will receive milestone and royalty payments as the technology develops further.

Steven Rosenberg, one of the NCI researchers developing the original technology, led this latest study. The article reports on a cancer patient with colorectal cancer expressing the KRAS G12 that spread to the individual’s lungs. After the treatment of the person’s modified T-cells, all 7 tumors in the lungs shrunk in size. After 9 months, however, the team found one of the tumors began growing again. Further investigation of the removed tumor showed the cancer cells mutated further to stop expressing the binding target for the modified T-cells.

The authors conclude that engineered T-cells can provide an effective immunotherapy against solid tumor cancers expressing KRAS G12D mutations. Rosenberg adds in an NCI statement that, “We have also identified multiple T-cell receptors that recognize this KRAS product, thus opening the possibility of T-cell receptor gene therapy against multiple types of cancer that express this common mutation.”

The authors note the study is a proof-of-concept and still needs to be tested in more patients. Kite Pharma says this case is one of the few where engineered T-cells treat solid tumor cancers. Other recent studies report the use of T-cells for immunotherapy against bile duct cancer.

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