An independent publication cites using HemaCare primary T-cells to investigate a novel cancer therapy based on blocking immune suppression while simultaneously promoting T-cell activity. 
Newly approved T-cell therapies have been eliciting enthusiastic discussion across the medical field for their unparalleled success rate in treating aggressive blood cancers. This success has unfortunately not extended to the treatment of brain tumors, where upregulation of the “immune checkpoint” molecule PDL-1 interferes with normal immune response. Now a research group based at the University of Alabama’s Medical School may have found a way to outsmart brain cancer cells that evade the body’s immune system.The researchers have been investigating a molecule referred to as MLN4924. This molecule is capable of crossing the blood-brain barrier, and blocking an enzymatic pathway that lets tumor cells multiply rapidly. The effect of MLN4924 is tumor cell-specific. Hypothetically, this is great news. Unfortunately, the act of shutting down this enzymatic pathway indirectly activates the immune checkpoint molecule PDL-1. PDL-1 in turn causes immune suppression, which interferes with T-cell activity against cancer cells, creating a Catch-22 situation.
Fortunately, that’s not the end of the story. The authors decided it was worthwhile to investigate the matter more closely, and see whether they could use MLN 4924 to block tumor cell proliferation, while at the same time preserving T-cell activity against tumor cells. To begin this research, they purchased whole blood from HemaCare, which they used as starting material for an expanded population of human T cells. High-quality cellular starting material is known to be a critical factor in achieving consistent research results.
The researchers first had to prove that MLN4924 worked as the authors claimed in their brain cancer model. By tracking PDL-1 expression in clinical brain tumor samples, a brain-tumor derived cell line, and a brain tumor mouse model, the researchers were able to verify PDL-1 overexpression following MLN4924 treatment in brain tumor versus normal tissue. They also showed that this PDL-1 overexpression helped protect tumors from T-cell based immunity. 
Next, the authors demonstrated that MLN4924 treatment triggered an increase in tumor-specific T-cell response. This response could be maintained in the presence of PDL-1 inhibitors, thus blocking tumor-induced immune suppression. These results proved that the strategy of using MLN4924 in combination with immune suppression inhibitors could potentially slow or stop brain tumor progression.
The presence of a brain tumor is one of the most dreaded and devastating diagnoses a person can receive. It is also one of the most expensive diseases to treat. While still in the exploratory stage, this new combination strategy could prove to be the advance that physicians need to bring a viable treatment for this disease to the clinic.
- Filippova N., et al. Blocking PD1/PDL1 Interactions Together with MLN4924 Therapy is a Potential Strategy for Glioma Treatment. J Cancer Sci Ther. 2018; 10(8): 190–197.
- Xue S., et al. The prognostic significance of PD-L1 expression in patients with glioma: A meta-analysis. Scientific Reports. 7: 4231. 2017.