Combo immunotherapy produces distinct waves of cancer-fighting T cells with each dose
Source: Penn Medicine News , August 2024
PHILADELPHIA – A new tool for monitoring immune health patterns over time has revealed how a pair of checkpoint inhibitor therapies works together to recruit new cancer-fighting T cells with every infusion. Findings from the use of the new tool, developed by researchers at the University of Pennsylvania Perelman School of Medicine and Penn Medicine’s Abramson Cancer Center (ACC), were published today in Cancer Cell. The study challenges fundamental assumptions about how a common immunotherapy drug combination activates different types of T cells to defeat cancer and could help researchers more precisely measure immune response in future clinical trials.
Immunotherapy has made immense progress in improving survival for advanced melanoma over the last decade, although researchers are still working to understand why some patients’ cancers respond better than others and to develop therapies that come with less side effects. This study focused on a particular immunotherapy combination that has become a mainstay of melanoma treatment: PD-1 and CTLA-4 checkpoint inhibitors.
A new understanding of T cell response
Immune checkpoint inhibitors work by unleashing T cells to find and kill cancer cells. It was thought that this type of combination immunotherapy works by equipping an army of T cells to recognize and fight cancer throughout the course of treatment. In a sense, the idea was that if this group of T cells stayed strong for long enough, they would conquer cancer, but if they became too depleted, they would lose the battle. The study, which analyzed data from 36 patients treated with immunotherapy for advanced melanoma, found that the combination therapy produces waves of new T cells—known as a clonal response—with each dose, rather than continually strengthening the same pool of T cells.