NCI Researchers Develop Innovative Approach to Significantly Boost T-Cell Therapies Against Solid Tumors
11-1-23 (by: Scott Gleason) In a significant breakthrough in cancer immunotherapy, researchers at the National Institutes of Health (NIH) have developed a novel approach that could significantly enhance the effectiveness of T cell-based immunotherapy treatments, particularly for solid tumors. This advancement has the potential to dramatically improve the effectiveness of these therapies.
T cells, a type of specialized white blood cell within the immune system, play a crucial role in identifying and eliminating abnormal or infected cells. T-cell therapies, such as CAR T-cell therapy, harness the power of these cells to target and destroy cancer. While CAR T-cell therapy has been highly successful in treating blood cancers, it has faced challenges when applied to solid tumors.
New research from researchers at the National Cancer Institute (NCI – part of the NIH), published on November 1, 2023, in Clinical Cancer Research, details how they engineered T cells, including CAR T cells and another form of cellular immunotherapy known as TCR T cells, to carry cytokines. Cytokines are proteins with the unique capability to enhance T-cell function. By integrating these cytokines into T cells, the researchers aimed to bolster their effectiveness against solid tumors.
In laboratory studies, the modified CAR and TCR T cells expressing the cytokines IL-15 and IL-21 on their surface demonstrated the ability to eliminate a significantly higher number of cancer cells compared to T cells with only one of these cytokines or none at all. Previous studies have identified that administering high quantities of cytokines to patients could lead to severe and potentially life-threatening side effects. The researchers’ differentiated approach seeks to deliver the cytokine boost in a more targeted and controlled manner.
In a mouse model designed to mimic cervical cancer, T cells carrying both cytokines successfully shrank tumors completely in 4 out of 5 mice. In contrast, only 1 out of 5 mice treated with T cells carrying a single cytokine experienced tumor reduction. Furthermore, the mice treated with T cells containing both cytokines exhibited an extended lifespan compared to those treated with T cells carrying only one cytokine. The approach also displayed significant promise in mouse models of pediatric neuroblastoma, a challenging and challenging-to-treat childhood cancer. When applied to these models, T cells with both cytokines were more effective at reducing tumor size compared to T cells with one or no cytokines. Importantly, in both cervical cancer and neuroblastoma models, T cells equipped with the cytokine pair did not induce any severe side effects. The researchers are now actively pursuing further investigations into the potential of IL-15- and IL-21-expressing T-cell therapies, conducting additional laboratory and animal model studies on various types of solid tumors. Their ultimate goal is to translate this pioneering approach into human clinical trials within the next few years.