Scientists use PBMCs from HemaCare to design experiments in cancer immunotherapy. Cancer stem cells become a target!
Cancer is on center stage with several breakthroughs. We reported on two vaccines that had remarkable outcome in patients with pancreatic cancer and brain cancer. Such progress is the result of years of research exploring how the immune system can be educated to recognize and remove tumors.
Immunotherapy has added to surgery, radiation, chemotherapy, and targeted drugs, but the focus has remained on eradicating tumors. Now, scientists are daring to think beyond the immediate need to shrink the tumor. What if we could eradicate residual disease and relapses through eliminating therapy-resistant cancer stem cells that are left behind in the patient?
A group of scientists from Cedars-Sinai Medical Center, Torrey Pines Institute for Molecular Studies, and ImmunoCellular Therapeutics came together to explore a regimen for targeting cancer stem cells, identified by the CD133 protein on their surface.
Could the CD133 protein be used in a vaccine to make cancer stem cells identifiable to the immune system? To answer this question, these scientists resorted to computer modeling. They used the “Immune Epitope Database” to predict which CD133 peptides (protein fragments) were potential epitopes (immune-reactive protein fragments) that could bind to MHC molecules.
MHC molecules are clasps on cell surfaces that present epitopes to T cells, and T cells in turn interact with MHC molecules. There are ~2000 alleles (gene variations) in the human population for 9 MHC molecules in every person. Different HLA alleles cause changes in HLA molecules at positions that impact either peptide binding or interactions with the T cell receptor, leading to stimulation/activation.
The research team turned to HemaCare for fresh apheresis units and peripheral blood mononuclear cells (PBMC) from donors positive for HLA-A*0201, a MHC-allele that is common in the US population. HemaCare products were used to isolate T cells and monocytes. Dendritic cells were cultured from monocytes and loaded with different CD133 peptides to test how well they bound to HLA-A*0201 MHC, and whether they could stimulate T cells.
Through elaborate experimentation involving bench assays and testing in mice, the researchers were able to identify two peptides from CD133 that served as strong epitopes for cancer stem cells. These epitopes loaded onto dendritic cells were recognized by T cells and stimulated them so that the T cells caused cell lysis when incubated with cancer stem cells. Furthermore, these epitopes did not cause any auto-immune reaction.
On the basis of their findings, this research group has initiated a phase 1 clinical trial in recurrent glioblastoma patients to test a dendritic cell vaccine using these CD133 epitopes. HemaCare is proud to have provided PBMC and apheresis units.
1. Ji J, Judkowski VA, Liu G, Wang H, Bunying A, Li Z, Xu M, Bender J, Pinilla C, Yu JS. Identification of novel human leukocyte antigen-A*0201-restricted, cytotoxic T lymphocyte epitopes on CD133 for cancer stem cell immunotherapy. Stem Cells Transl Med. 2014 Mar; 3(3):356-64.