The journal "Science" has published the results of a phase 1 clinical trial during which patients were modified with immune T cells using the CRISPR-Cas9 technique. The information presented demonstrates the preliminary safety of using the CRISPR-Cas9 genetic engineering technique in humans to treat advanced, resistant cancers.

The Phase 1 clinical trial (clinicaltrials.gov, NCT03399448) was designed by a team from the University of Pennsylvania in collaboration with the Parker Institute for Cancer Immunotherapy and Tmunity Therapeutics. The primary objective of the clinical trial was to demonstrate the safety profile of a single infusion of CRISPR-Cas9-modified T cells.

The target population was three patients: those with advanced refractory myeloma (two patients) and those with metastatic sarcoma (one patient).

T cells of the immune system - T lymphocytes - were collected from the patients. Using the CRISPR-Cas9 method, the cells were genetically modified by modifying the TRAC, TRBC1, TRBC2 and PDCD1 genes (encoding the PD-1 receptor) to improve anti-tumour immunity. Subsequently, cells were transduced with a vector containing the NY-ESO-1 transgene to enhance cancer cell recognition. 

Participants in the clinical trial were given lymphodepleting chemotherapy (cyclophosphamide and fludarabine on days -5 to -3 (i.e. prior to CRISPR-Cas9 administration) and a single infusion of modified T cells at a dose of approximately 100 million cells per kilogram of body weight on day 0.

Pilot clinical trials have demonstrated the preliminary safety and feasibility of multiplexed CRISPR-Cas9 human T-cell genome engineering in patients with advanced, refractory cancer.

The T cells were well tolerated by the body. It was noted that the level of modified T cells after infusion remained constant throughout the study period i.e. 9 months. This was also confirmed by bone marrow and tumour biopsies, where genetically modified T cells were shown to be present in all patients.

The researchers state, "Although the preliminary results of the clinical trial have an acceptable level of safety, experience with a larger number of patients undergoing infusions of CRISPR-engineered T cells with higher editing efficacy with longer post-infusion follow-up will be required to fully assess the safety of this approach."

Material was prepared by: Andrzej Jamkowy

Source: Science

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