Over the years, a prime mission of this blog has been to highlight advances in cancer research. Now, we have good news regarding new research on waking up T cells. Still in the early stages. But promising.
From Novartis and the University of Penn: New Research on Waking up T Cells
CAR-T treatments like Novartis’ Kymriah have proven effective in some B-cell-driven cancers. With one notable exception: chronic lymphocytic leukemia (CLL). Now, researchers at the University of Pennsylvania, which pioneered the CAR-T technology that formed the backbone of Kymriah, are proposing a new method for overcoming CAR-T resistance in CLL.
The Penn team demonstrated that they could improve the function of CAR-T cells. How? By inhibiting bromodomain and extra terminal (BET) proteins. Blocking BET helped combat “T cell exhaustion.” That is a well-known phenomenon that prevents engineered CAR-T cell treatments from fully attacking CLL. They reported in the Journal of Clinical Investigation. Novartis, which has a licensing arrangement with Penn, was one of the backers of the study, along with the National Cancer Institute and several other groups.
CAR-T treatments, made from patients’ own immune cells, have been about 80% effective in acute lymphocytic leukemia (ALL). Often curing advanced forms of the disease. But only a small fraction of CLL patients have responded well to CAR-Ts in clinical trials.
So, how could the Penn discovery apply to CAR-T development for CLL? The researchers suggested that JQ1 could be used to improve the engineering and expansion of CAR-T cells made for CLL patients. Many of whom will start the treatment process after their T cells are worn down by chemotherapy. “Treating these ‘war weary’ T cells during the CAR-T cell engineering process with the potential to boost responses,” said senior author Joseph Fraietta, P .D., an assistant professor of microbiology at Penn, in a statement.
The following chart highlights the research process. As it appears in the Journal of Clinical Investigation article.