By Kim Polacek, APR, CPRC - February 10, 2020
CRISPR gene editing has been a controversial topic in the science community. The technology allows researchers to easily alter DNA sequences or modify gene functions. It gives them the potential to correct genetic defects or treat and prevent the spread of diseases such as cancer. But ethical and safety concerns have slowed or halted scientific studies using the technology.
Now for the first time in the United States, a clinical trial has been completed using CRISPR and provides evidence that the technology could be beneficial in improving cellular immunotherapies for cancer patients. Researchers at Abramson Cancer Center of the University of Pennsylvania used CRISPR to enhance T cell receptor (TCR) therapy, a treatment where T cells are taken from a patient and genetically modified in a lab to add a receptor to the cells so they can better recognize and attack tumors. In this study, CRISPR was used to make three edits to the T cells before modification. The edits removed receptors and a checkpoint that can often inhibit T cells from working properly to detect and kill cancer cells.
The purpose of the study was to determine whether CRISPR edited and receptor enhanced T cells could safely be given to patients and survive once inside the body. The researchers infused three patients — two with multiple myeloma and one with sarcoma. Not only was the therapy well tolerated, the enhanced cells were still in bloodstream nine months later.
“A note of caution is that CRISPR mediated editing can, theoretically, have off target effects with damaging consequences. The use of specific guides and very careful optimization of deletion procedures will be a requirement when different genes are simultaneously edited, to avoid the theoretical possibility of secondary hematological malignancies that could arise from adoptively transferred cells,” said Conejo-Garcia.
Moffitt is also looking at utilizing CRISPR edited T cells for cellular immunotherapy. Conejo-Garcia and his team are developing a study integrating chimeric antigen receptors into places left open by CRISPR mediated cuts. They hope to launch by the end of the year.