First-in-Human Trial of CRISPR-Cas9 Begins in Lung Cancer Patients

A hospital in China has made history by injecting a patient with lung cancer with revolutionary, yet controversial, CRISPR-Cas9—edited T cells, according to a news report in Nature. The first patient was injected on October 28.

The phase 1 trial, registered on ClinicalTrials.gov as NCT02793856, aims to evaluate the safety of programmed death ligand-1 (PD-1)—knockout T cells in metastatic non-small cell lung cancer (NSCLC). This dose-escalation study will evaluate the PD-1–knockout T cells in 10 stage IV patients with NSCLC who have progressed on all standard treatments at West China Hospital, Sichuan University, China. T cells from these patients will be isolated to delete the gene for PD-1, which encodes the PD-1 protein—the checkpoint in T cells that prevents the body from initiating an immune response against cancer cells. Patients will receive anywhere between 2 and 4 injections of the T cells, and will be monitored for a 6-month period.

PD-1 is targeted by both nivolumab (Opdivo) and pembrolizumab (Keytruda).

The key to using this technology is post-editing cell validation—CRISPR is known to have errors that can insert edits in the wrong places on the genome. In China, a biotechnology company called MedGenCell is expected to validate the cells to ensure that the right genes have been knocked down, before the cells are reintroduced into patients.

Lu You, MD, an oncologist at Sichuan University who is leading the trial, told Nature that the first round of treatment was smooth, and the patient is expected to receive another injection. Lu also shared that his team will follow the patients beyond the 6 months indicated in the protocol to document any treatment benefits.

Meanwhile, similar efforts are ongoing in the United States, led by Carl June, MD, an immunologist at the University of Pennsylvania. This summer, a federal biosafety and ethics panel gave the green light to the first such study in humans, although the trial is yet to receive FDA approval. The trial, expected to begin in 2017, will enroll patients diagnosed with multiple myeloma, melanoma, and sarcoma for a safety analysis, similar to the trial in China. The US trial will also use CRISPR to knockout 2 genes: PD-1 and endogenous T-cell receptor, to improve treatment efficacy.

Trial sites include the University of Pennsylvania, the MD Anderson Cancer Center, and the University of California, San Francisco.