Off-the-Shelf PSCA-Targeted CAR-NK Therapy Advances to Clinical Trials for Pancreatic Cancer

Pancreatic Cancer, is a highly malignantDiagnosisBoth diagnosis and treatment are challenging for malignant gastrointestinal conditions.Tumor。

In recent years, the incidence and mortality of pancreatic cancer have significantly increased. The early diagnosis rate of pancreatic cancer is not high, and it is often already in the advanced stage when discovered. At this point, the cancer cells have already spread. Although some chemotherapy drugs are effective, drug resistance often develops, and cancer immunotherapy is also difficult to apply. The 5-year survival rate of pancreatic cancer is less than 10%, making it one of the malignant diseases with the worst prognosis.Tumor, thus it is also called the "King of Cancers."

According to the latest data from the WHO, pancreatic cancer was the 7th most common cancer in China in terms of incidence (with an estimated 120,000 new cases in 2020) and the 6th most common in terms of mortality (with an estimated 120,000 deaths in 2020).

Recently, City of Hope National Medical Center, a world-leading cancer research and treatment institution, and CytoImmune Therapeutics, a cell therapy innovation company, collaborated to publish a preclinical study titled "Off-the-shelf PSCA-directed chimeric antigen receptor natural killer cell therapy to treat pancreatic cancer" in Gastroenterology, a top journal in the field of gastroenterology.

The engineered CAR-NK cell therapy (PSCA-CAR_s15-NK) developed in this study, derived from umbilical cord blood, showed significant efficacy in a mouse model of human metastatic pancreatic cancer. The therapy enabled sustained survival in mice for over 90 days, significantly extended their lifespan, and demonstrated no treatment-related toxicity. This preclinical study supports the therapy's advancement into human trials this year.Clinical Trial。

Approximately 60%-80% of pancreatic cancers highly express prostate.Stem CellsProstate Stem Cell Antigen (PSCA), therefore, the research team chose to construct PSCA-CAR, in addition to knocking in secretory IL-15 to maintain the survival of NK cells. The CAR-NK cells used in this study underwent a freeze-thaw process, indicating that this allogeneic CAR-NK therapy can serve as a novel "off-the-shelf" cell therapy.

The research team believes that this CAR-NK therapy is highly promising for pancreatic cancer treatment for two reasons: first, the therapy is based on a precision medicine approach, targeting the specific antigen PSCA found in pancreatic cancer patients; second, it is an immunotherapy that uses engineered human natural killer cells, modified to specifically attack cancer cells.

In addition, except for pancreatic cancer, gastric cancer, prostate cancer and other solid tumorsTumorSimilarly high expression in the prostateStem CellsProstate Stem Cell Antigen (PSCA), therefore, this CAR-NK cell therapy is also promising for gastric cancer and prostate cancer.

The study was led by Professor Yu Jianhua and Professor Michael Caligiuri. Professor Yu is the founding director of the NK Cell Biology Research Program at the T Cell Immunotherapy Center of City of Hope National Medical Center, specializing in NKCell Biology, CAR-NK, CAR-T, oncolytic virus, bispecific antibody and other fields have made many important breakthroughs.

Professor Michael Caligiuri is the president of City of Hope National Medical Center, former president of the American Association for Cancer Research (AACR), and a world-renowned medical scientist. He was elected as a member of the National Academy of Medicine for his groundbreaking discoveries in the field of NK cells. His research has paved the way for CAR-NK cell therapy to enter clinical trials. To date, more than 1,000 cancer patients have received NK cell treatments designed or co-designed by Michael Caligiuri.BioValleyBioon.com）