Cytovia, NCI Team Up to Develop CAR NK-cell Therapy for Solid Tumors

Cytovia, NCI Team Up to Develop CAR NK-cell Therapy for Solid Tumors

Cytovia Therapeutics has entered into a licensing agreement with the National Cancer Institute (NCI) to develop a new “off-the-shelf” immunotherapy for solid tumors.

The immunotherapy is based on “natural killer” or NK immune cells, which have been genetically modified to produce a chimeric antigen receptor, or CAR, that targets a specific cancer protein, Cytovia said in a press release detailing the new collaboration.

The agreement licenses to NCI the use of NK cells modified to target glypican-3 (GPC3), a protein found at high levels in hepatocellular carcinoma cells, one of the main types of liver cancer, as well as other solid tumors.

GPC3 controls the Wnt signaling pathway, which is essential during embryonic development of the liver and the kidney but is mostly “turned off” in adult cells. However, cancer cells can reactivate this pathway, leading to uncontrolled division and suppression of the immune response.

The NK cells are derived from a line of induced pluripotent stem cells (iPSCs), fully matured cells that can be reprogrammed back to a stem cell state, where they are able to grow into any type of cell.

Unlike other CAR NK-cell therapies that require researchers to collect a patient’s own NK cells, iPSCs represent a renewable source for the large-scale and cost-effective production of off-the-shelf NK therapies.

The new GPC3 CAR NK-cell therapy couples Cytovia’s gene-edited iPSC-derived NK cell technology with a CAR receptor developed by Mitchell Ho, PhD.

Ho, the director of the antibody engineering program and deputy chief of the laboratory of molecular biology at the NCI Center for Cancer Research, had previously developed humanized CAR receptors targeting the GPC3 protein that helped T-cells eliminate liver cancer cells.

“Natural Killer cells play a major role in the immuno-surveillance of liver cancer. GPC3 is expressed in more than 70% of hepatocellular carcinoma cells but not on healthy cells,” Ho said.

“We look forward to investigating whether GPC3 CAR-NK therapy could provide a new safe and effective off-the-shelf option for patients with liver cancer,” Ho said.

Cytovia and NCI also have established a Cooperative Research and Development Agreement (CRADA), under which the company will collaborate with Ho’s lab to further advance the clinical development of the new immunotherapy.

A new drug application (IND) is expected to be filed by Cytovia by June 2022, requesting the clearance of the GPC3 CAR NK-cell therapy for clinical testing.

“GPC3 is an exciting new validated target for hepatocellular carcinoma, an area of major unmet medical need, as well as other solid tumors,” said Daniel Teper, chairman and CEO of Cytovia.

“We look forward to collaborating with Dr. Ho, a pioneer in GPC3 research, to develop a novel gene-edited, iPSC-derived GPC3 CAR NK that will advance toward a cure for liver cancer,” Teper said.