Next-generation CAR-T therapy shows promising results for advanced liver cancer
A recent study presented at the American Society of Clinical Oncology Annual Meeting (ASCO 2024) showed that a new next-generation CAR-T therapy called C-CAR031 could potentially offer hope for patients with advanced hepatocellular carcinoma (HCC).
Understanding Hepatocellular Carcinoma (HCC)
Hepatocellular Carcinoma (HCC) is the most common type of liver cancer that typically results from chronic hepatitis B or hepatitis C, fatty liver disease, heavy alcohol consumption, and other causes. It is often detected late and can be difficult to treat as it generally does not respond well to chemotherapy. Standard treatment may involve targeted therapy and checkpoint inhibitor immunotherapy.
The Role of CAR-T Therapy
Chimeric antigen receptor T-cell therapy, also known as CAR-T therapy, is a next-generation immune system-based treatment that reprograms a patient’s own T cells by inserting a synthetic receptor that recognizes their cancer. This process involves removing a sample of an individual’s white blood cells, reprogramming T cells to attack their cancer, manufacturing a large quantity of the modified cells, and infusing them back into the body. While several CAR-T therapies have been approved for blood cancers such as leukemia and lymphoma, this approach has not worked well for solid tumors.
C-CAR031: The Next Generation CAR-T Therapy for Treating HCC
C-CAR031 is designed by AstraZeneca and manufactured by AbelZeta in China. It targets GPC3, a surface antigen heavily expressed in liver tumors, but usually absent in healthy tissue. It is a so-called “armored CAR” designed to fend off an immunosuppressive cytokine (TGF-beta) that can turn off T-cell activity. C-CAR031 was custom-made using T cells from each patient.
C-CAR031 Study Results and Safety Profile
After undergoing strong chemotherapy to kill off their existing immune cells and make room for the new ones, each participant received a single IV infusion of the CAR-T therapy at one of four dose levels. After a median nine months of follow-up, 91% of the 23 evaluable patients saw some reduction in tumor size, both in the liver and in metastatic lesions. The objective response rate, meaning tumors shrank by a specified amount, was 57% overall across all dose levels and increased to 75% for those in the highest dose group. The disease control rate, meaning tumors either shrank or remained stable with no further progression, was 91%. Based on this early data, the estimated median overall survival time is about 11 months.
Side effects were common but generally manageable. Many adverse effects were attributable to the preparatory chemotherapy, including reduced lymphocyte counts, neutropenia, and low platelets. Introducing engineered T cells can trigger a strong immune reaction known as cytokine release syndrome (CRS), and neurologic toxicity. However, no dose-limiting toxicities or neurologic toxicity was observed in the study. Most patients developed CRS, but only one case was considered severe (Grade 3 lung inflammation). All adverse events were ultimately reversible.
The Future of C-CAR031
Based on the study’s findings, AstraZeneca, and AbelZeta are planning to advance C-CAR031 into an international Phase II trial that will include sites in the United States. If the future results hold up, this could be one of the first next-generation CAR-therapies that work well against solid tumors.
Conclusion
The study showed a promising efficacy of C-CAR031 in advanced hepatocellular carcinoma (HCC) patients. While its safety profile was manageable, patients may experience common side effects such as cytokine release syndrome.
Overall, C-CAR031 showed potential to bring clinical value and offer hope to patients with limited treatment options.
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Originally Post From https://www.cancerhealth.com/article/armored-cart-therapy-shows-promise-liver-cancer
