The biomedical world was revolutionized by the introduction of clustered regularly interspaced short palindromic repeats (CRISPR) gene-editing technology, which may soon have cancer immunotherapeutic applications. Human trials of the technology are drawing nearer, as an advisory committee at the National Institutes of Health recently approved a proposal that would use CRISPR-Cas9 to bolster cancer immunotherapies based on mobilizing a patient’s own T cells to destroy tumors.
Such cell therapies for the treatment of cancer are rather promising, but some patients continue to struggle with relapse. The researchers behind the human trials hope that gene editing could improve the efficacy of the immunotherapies and address some of the major issues preventing these treatments from being as effective as possible.
The Upcoming American CRISPR Trial
The first trial will not involve many patients, as the primary aim of the research is to prove that CRISPR is safe for use in humans. Further trials will be conducted to judge the technology’s ability to treat cancer and bolster existing treatment options. Funding for the trial comes from the immunotherapy foundation started by the former president of Facebook, Sean Parker. The Parker Institute for Cancer Immunotherapy has $250 million at its disposal to fuel the research, but the trial itself does not yet have a budget.
CRISPR is now being used in a wide range of experiments on subjects other than humans. However, given the sophistication and expense associated with utilizing this technology high value therapeutic targets for humans are of most interest. The tool has the potential to permanently alter the human genome in a way that will be passed down to future generations. Scientists earlier this year convened in Washington, DC, to create an agreement that outlaws use of the technology for human genetic engineering. However, the technology can still be used in the treatment of cancer.
How Can CRISPR Treat Forms of Cancer?
While CRISPR itself is not a therapy, it provides a unique tool for improving the groundbreaking therapies now being tested. CRISPR has the potential to make genetic edits in an effective, reliable manner. The genetic edits in a patient with cancer would, theoretically, trigger the immune system to attack the tumor.
The American trial intends to test CRISPR in the treatment of melanoma, myeloid cancers, and sarcoma. Another team in China will also soon undertake preliminary clinical trials in the use of CRISPR in the treatment of non-small cell lung cancer. Both teams plan to take an approach that involves first harvesting T cells from the blood of the patient and then modifying the genes using CRISPR, with the purpose of activating T cells against cancer cells. Once this has been accomplished, the cells will be introduced back into the body of the patient so that they can target the cancer.
The Concerns Involved with CRISPR Technology
While much excitement surrounds the upcoming trials, especially since they will pave the way for future experimentation, the real possibility of failure still exists. The real worry involving CRISPR is the risk of unintended consequences, especially if the technology makes unpredictable genetic edits in undesignated places. Genetic edits could potentially trigger a catastrophic immune response, called a cytokine storm, which can be fatal. Another worry is that the mobilized T cells will begin attacking healthy tissue.
The American CRISPR trial will take place at the University of Pennsylvania. A total of three CRISPR edits will be conducted on T cells taken from 18 patients who have been diagnosed with one of the three forms of cancer mentioned above. One edit inserts a gene for a protein designed to detect cancer cells and direct the T cells to attack them. The next edit removes a natural T cell protein that has the potential to interfere in this process. The final edit removes the gene that codes a protein used by cancer cells to detect and disable T cells. The cells will be infused back into the patients to determine toxicity.
Other Forms of Genetic Editing Being Tested
CRISPR is not the first genetic editing technology used to fight disease. In 2014, zinc-finger nuclease technology was used in a small trial involving 12 patients with HIV. An engineered protein was used to remove a gene that encodes a certain T cell protein targeted by the virus. The trial had promising results in preventing infection of new cells, and the technique has been used in other clinical trials for a range of conditions.
Also, researchers at a London hospital recently began a trial with 10 children to test a gene-editing technique called TALENS. This system uses T cells from a donor, rather than the patient. The cells are edited to prevent rejection and to direct T cells to attack cancer cells. Edits are also intended to protect T cells from damage by other immunotherapy drugs used in combination with genetic editing.
CRISPR is easier to use than these technologies and has more potential for editing multiple genes, but the technique has been known to create off-target edits. This issue will be the largest hurdle to overcome if the upcoming clinical trial approves using CRISPR in human patients with cancer.