Researchers have developed a bone marrow-derived stem cell line capable of boosting the effectiveness of immune-based CTLA-4 therapy in mice. This finding indicates that the stem cell lines may also present resistance to other CTLA-4 checkpoint inhibitors.
CTLA-4 checkpoint inhibitors are a class of drugs that block a specific protein used by the CD4 T cells or T-regulatory cells to detect cancer cells. During therapy these checkpoint inhibitors induce what is termed a memory T cell phenotype-a modification that enables the CD4 T cell to recognize and attack cancer cells when they arise in the body.
However the effector cells can develop resistance. One such resistant mechanism is detected by enhanced expression of p53-related CD4 T cells. Yet immunotherapy with CD4 T cells is not generally successful in patients due to resistance in p53-related CD4 T cells. Thus researchers have been searching for p53-related CD4 T cells.
In a series of laboratory studies researchers were able to detect the presence of p53-related CD4 T cells with the help of bone marrow thyroid and mesenchyme extract. The results indicate that the use of bone marrow-derived mesenchyme stem cells (MSCs) to enable boosting of CD4 T cell immunotherapy could become a promising new avenue for enhancing the success of immunotherapy in patients with chronic weakened immune systems.
KoiGray a research team of Professor Naoki Iwata of Tetsuya Hospital University of Tokyo and his research team employed mouse models for the development of inflammatory bowel diseases and metastatic colorectal cancer. In this endeavor the researchers successfully induced CD4 T cells to emerge in the mice to mimic the process of spontaneous CD4-transplanted T cells in human colorectal cancer. The team subsequently administered a class of drugs that blocked CD4 T cell signaling-a combination of drugs that causes fewer cells to begin a programmed cell death called programmed cell death.