Researchers at the University of Pennsylvania Philadelphia are treating two patients with cancer using CRISPR. One patient has sarcoma, cancer that forms in the muscles, nerves, and surrounding joint tissue, and the other patient has multiple myeloma, cancer that develops in the bone marrow and pushes out healthy protein. The experimental treatment uses CRISPR to edit the genes in T-cells extracted from the patients. The genes of the T-cells are edited in the lab and then reintroduced to the patient's body, with the expectation that the T-cells will target cancerous cells with high-efficiency. CRISPR gene-editing has advanced significantly in the last few years. In 2017, CRISPR was used to correct overly thick heart muscles in human embryos, and in 2018 antioxidant genes were reintroduced to high-yield tomato plants. Despite these advances that have increased confidence in gene therapy, researchers will not be releasing any results for the foreseeable future, so as not to encourage others to pursue this treatment option until scientists better understand any adverse effects.
T-cells are human immune cells that monitor for abnormal protein expression, commonly caused by germs and cancer. The procedure would involve removing some of these cells from the patient and editing the DNA with CRISPR/cas9 in the lab. Editing the DNA in the lab then returning the cells into the body, reduces the risk of mistakes by the cas9 protein. Scientists are making two changes to the T-cells' DNA; the PD-1 gene gets deleted, and the TCR gene gets optimized. The PD-1 gene is a checkpoint before deploying immune defenses, so T-cells do not attack healthy cells. By removing this checkpoint, the T-cells will more rapidly synthesize an immune response against cancerous cells. The TCR gene is responsible for recognizing abnormal patterns in the peptides on the surface of cells. By optimizing this gene to look for the peptide patterns caused by cancer, the T-cells can find and attack cancerous cells with high efficiency.
Despite this experiment embodying what medical researchers have wanted to do with CRISPR since it's debut in 2012, researchers are steadying their pace. In 1999, a patient died as a result of a gene therapy trial at the University of Pennsylvania. Technology and understanding of gene therapy have greatly advanced in the last two decades, but CRISPR is a powerful tool that requires great responsibility from scientists and doctors.
Eventually, the CRISPR trial could include up to eighteen cancer patients, but researchers are treading carefully. Updates about the experiment will not be released until the researchers feel that the risk of unintended effects is no longer likely. When results are made public, it will be via medical meeting presentation or peer-reviewed published paper.