Chimeric antigen receptor (CAR) and T-cell receptor (TCR) T-cell therapies are only effective in a subset of patients with solid tumors, but researchers are now in need of new approaches to universally improve the prognosis of patients treated. A recent article published in the international journal Clinical Cancer Research entitled "Cooperative armoring of CAR and TCR T-cells by T cell-restricted IL-15 and IL-21 universally In the study entitled "Cooperative armoring of CAR and TCR T-cells by T cell-restricted IL-15 and IL-21 universally enhances solid tumor efficacy" in the international journal Clinical Cancer Research, scientists from the National Institutes of Health (NIH) and other institutions developed a new approach that may potentially enhance the efficacy of T-cell-based immunotherapies, such as CAR-T-cell therapies, in the treatment of solid tumors.
T-cells are specialized white blood cells in the immune system that eliminate infected or abnormal cells, and in animal studies, this enhanced T-cell therapy may be effective against human cervical cancer and neuroblastoma, a common solid tumor in children.CAR-T-cell therapy is a specific type of cellular immunotherapy that focuses on engineering T-cells from a patient's body in the laboratory To improve the efficacy of T-cell therapy against solid tumors, researchers have engineered T cells (CAR-T cells and another type of cellular immunotherapy called TCR-T cells) to carry cytokines, special proteins that enhance the function of T cells. T-cell function.
In laboratory studies, both CAR and TCR T cells can be modified to express the cytokines IL-15 and IL-21 on their surfaces, which would have to kill far more cancer cells than T cells carrying only one of the two cytokines or none of the cytokines; previous findings have suggested that treating patients with large amounts of cytokines may cause serious and potentially fatal side effects, and this new approach aims to promote cytokine production in a more targeted way. new approach aims to boost cytokine production in a more targeted way. In a mouse model of cervical cancer, T cells carrying both cytokines caused tumors to shrink completely in four out of five mice, compared with one out of five mice treated with a single cytokine; mice treated with T cells carrying both cytokines may live longer than mice treated with T cells carrying only one cytokine.
This therapy also showed great therapeutic potential in mouse models of pediatric neuroblastoma, a refractory childhood cancer that desperately needs novel therapies, where T-cell therapy with two cytokines may be able to induce tumor shrinkage in the body to a certain extent compared to T-cells carrying only one growth factor or no growth factor, and in models of cervical cancer and neuroblastoma. T cells carrying both cytokines did not induce any serious side effects in the body. Researchers are currently continuing their studies to test the efficacy of T-cell therapies expressing IL-15 and IL-21 in laboratory and animal model studies of other solid tumors, with the goal of translating this approach into human clinical trials in the coming years.
Taken together, the results of this paper suggest that co-expression of membrane lineage IL-15 and IL-21 represents a technology that can enhance the plasticity and function of engineered T cells against solid tumors, and may hold promise for application to multiple therapeutic platforms and in the study of human disease.
