Human CRISPR Trials Could Become Sputnik 2.0

    It was the injection heard around the world. On October 28^th, a team of scientists at Sichuan University in Chengdu, China, delivered the first cells that had been genetically altered using the revolutionary genome-editing technique called CRISPR (clustered regularly interspaced short palindromic repeats) into a human patient with aggressive lung cancer.  While it initially looked as though the U.S. would be the first to the “party,” with human clinical trials using CRISPR to target three genes involved in various cancers is slated to begin in early 2017, the Chinese researchers leap-frogged the line.

    “I think this is going to trigger “Sputnik 2.0,” a biomedical duel on progress between China and the U.S., which is important since competition usually improves the end product,” remarked to Nature News. Dr. June is a professor of immunotherapy at the University of Pennsylvania and the scientific adviser for the upcoming U.S.-based CRISPR clinical trials. Shortly after the start of the U.S. trial—early in 2017—a group of investigators at Peking University, Beijing, is optimistic about starting three clinical trials in March 2017 using CRISPR against bladder, prostate, and renal cell cancers. However, funding for those trials has yet to be approved.

    In the Sichuan University study, led by Lu You, M.D., an oncologist at the university’s West China Hospital, the researchers removed immune cells from the recipient’s blood, disabling an immune cell gene using the CRISPR/Cas9 system, which consists of an endonuclease (Cas9) and a molecular guide RNA that can be programmed to tell the enzyme precisely where to cut. In the current study, the disabled gene codes for the protein programmed cell death 1 (PD-1), which normally puts the brakes on a cell’s immune response; cancers take advantage of that function to proliferate. PD-1 is a frequent target of checkpoint inhibitor compounds that have seen recent success in treating several types of cancer.

    The research team cultured the edited cells, allowing them to proliferate and increase in number, and injected them back into the patient, who has metastatic non-small-cell lung cancer. The hypothesis is that without PD-1 the edited cells will be able to attack and destroy the cancer.

    The Sichuan team is optimistic about their patient, stating that the initial treatment went smoothly and that a second injection will be given soon. Moreover, the researchers plan to treat a total of 10 people, who will each receive between two to four injections. The scientists told Nature that the trial’s primary concern was for safety and that participants will be monitored for 6 months to determine whether the injections caused any serious adverse effects. Dr. Lu and his colleagues will continue to follow the patients beyond the 6-month time point to determine if they seem to be benefiting from the treatment regimen.

    Many scientists can’t help but be excited by CRISPR’s arrival into the clinical realm. “The technology to be able to do this is incredible,” Naiyer Rizvi, M.D., of Columbia University Medical Center in New York City told Nature. Additionally, Antonio Russo, M.D., of Palermo University in Italy noted that antibodies neutralizing PD-1 have successfully put lung cancer in check, boding well for a CRISPR-enabled attack on the protein. “It’s an exciting strategy, and the rationale is strong,” Dr. Russo remarked.

    Yet, researchers still urge caution in overinterpretation, and some question whether this trial will succeed. Dr. Rizvi told Nature that the Sichuan team’s method of extracting, genetically modifying, and multiplying cells is “a huge undertaking and not very scalable. Unless it shows a large gain in efficacy, it will be hard to justify moving forward,”—doubting that it will be better than current antibody therapies, which can be expanded to unlimited quantities in the clinic. Dr. Lu said that this question is being assessed in the trial, but only time will tell as to which is the best approach.