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Natural Killer Cells Stop Ovarian Cancer in Preclinical Test

Natural killer cell

Natural killer cell (NIAID, Flickr)

11 Apr. 2022. Results from a lab study show engineered immune system cells sharply reduce tumors and extend survival in mice grafted with a type of ovarian cancer. A team from biotechnology company Catamaran Bio Inc. in Boston presented the findings yesterday in a poster session at the American Association for Cancer Research annual meeting in New Orleans.

The researchers tested Catamaran Bio’s lead product code-named CAT-179 designed as a treatment for breast, gastric and other solid-tumor cancer. The company develops cancer treatments based on natural killer cells in the immune system. Like B- and T-cells, natural killer cells are white blood cells, which act against cells infected by viruses and in early-stage tumors. Catamaran’s technology, called Tailwind, alters donated natural killer cells — not the patient’s own immune cells — to express chimeric antigen receptors, or CARs, proteins attracting antibodies that bind to and destroy blood-related and solid tumor cancer cells.

Catamaran Bio says therapies are derived from natural killer or NK cells given by healthy donors, then engineered for signaling inside cells, to produce more immune-system enzymes aimed at tumors. The company says it programs CAR-NK cells to sense and evade the microenvironment that surrounds and supports tumors, and suppresses immune system activity against tumors. Also, says Catamaran, CAR-NK cells can carry larger genetic payloads that boost delivery of complex, multi-stage cancer treatments.

CAT-179 is engineered to express a large, complex NK cell payload, with CAR proteins, as well as transforming growth factor-beta with dominant-negative receptor (TGF-beta DNR) and Interleukin-15 or IL-15 proteins that aid cancer immunotherapies. In this study, researchers tested CAT-179 in lab cultures and mice grafted with human tumors over-expressing the protein human epidermal growth factor receptor 2 or HER2, found in aggressive ovarian and breast tumors.

98 percent tumor reduction

In preliminary lab tests, the team found CAT-179 remains stable and persistent, delivering 45 percent of NK-CARS after 14 days, helped along by IL-15. In addition, lab test results show CAT-179 produces interferon gamma, a protein that simulates an immune response, and resists suppression of immune responses from TGF-beta often found in tumor microenvironments.

The researchers then tested CAT-179 in lab mice with HER2-positive ovarian cancer tumors. The mice received either three CAT-179 injections or a saline solution seven days apart. Results show tumors in mice receiving CAT-179 reduce in size by 98 percent compared to saline solution recipients. And CAT-179 recipient mice survive for a median of 114 days, while saline recipients survive for a median of 60 days.

Vipin Suri, Catamaran’s chief scientist, says in a company statement that the results demonstrate “capabilities of our Tailwind platform to engineer off-the-shelf CAR-NK cell therapies with the features to overcome critical barriers to treat solid tumors. Suri adds, “We are successfully integrating NK cell engineering with scalable and efficient cell processing and manufacturing to deliver on the promise of off-the-shelf CAR-NK cell therapies for solid tumors,” and advancing CAT-179 to clinical trials.

Science & Enterprise reported on Catamaran Bio’s formation in November 2020, where it raised $42 million in its first venture round. The company is spun-off from medical school labs at University of Minnesota and George Washington University.

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