CD276-targeted Chimeric Antigen Receptor T Cells in Treatment With Advanced Pancreatic Cancer

Traditional treatments have limited efficacy in patients with pancreatic cancer, and molecular targeted therapy also has limited benefits. According to the results of the CONKO-005 clinical trial, compared with the single-agent Gemcitabine (Gemcitabine) treatment, the combined use of Erlotinib (Erolotinib) did not prolong the survival time of pancreatic cancer patients in postoperative adjuvant treatment. However, another phase III clinical result for patients with advanced pancreatic cancer found that compared with gemcitabine monotherapy, the survival of patients in the combined gemcitabine and erlotinib treatment group was significantly improved (6.24 months VS 5.91 months). The one-year survival rate has also improved (23% VS 17%). As a result, the FDA approved the "gemcitabine + erlotinib" combination regimen in 2005 for patients with locally advanced unresectable pancreatic cancer or distant metastases. However, this program only improves survival for about 10 days, making it difficult for the targeted drug erlotinib to achieve greater clinical benefit in the treatment of pancreatic cancer. In February 2019, the FDA approved olapa, an inhibitor that targets poly-ADP ribose polymerase, for the maintenance treatment of patients with metastatic pancreatic cancer who carry BRCA gene mutations, and then the population of patients with metastatic pancreatic cancer who carry BRCA gene mutations The limited quantity limits the scope of clinical application of olaparib. Therefore, it is necessary to explore new anti-pancreatic cancer therapeutic targets. CD276 (B7-H3) is a member of the B7 costimulatory molecule family. Its mRNA is widely expressed in tissues, but the protein expression is limited. It is expressed in resting fibroblasts, endothelial cells, osteoblasts, amniotic fluid stem cells and other non-immune cells, and The surface of induced antigen-presenting cells and NK cells. Many studies have revealed that B7-H3 is overexpressed in a variety of tumors, including melanoma, pancreatic cancer, breast cancer, prostate cancer, colorectal cancer and other tumors, and its expression level is closely related to the poor prognosis and clinical outcome of patients . Preclinical studies have confirmed that the expression of CD276 mRNA in pancreatic cancer tissues is significantly higher than that of normal adjacent groups.