12 November 2019

Early results from the first US trial to treat cancer patients using their own immune cells edited with CRISPR/Cas9 technology have shown the procedure to be safe, researchers will report.

Researchers from the Abramson Cancer Center of the University of Pennsylvania have so far infused three participants in the Phase I trial – two with multiple myeloma and one with sarcoma. They have observed the edited T cells expand and bind to their tumour target with no serious side effects.

Dr Edward Stadtmauer, section chief of haematologic malignancies at Penn and the study’s principal investigator, said the trial focuses on three prime aspects: if T cells can be edited in this specific way, if the resulting T cells are functional, and if the cells are safe to infuse into a patient.

He will present the findings from the study, which was conducted with the Parker Institute for Cancer Immunotherapy (PICI) and Tmunity Therapeutics, next month at the 61st American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida.

Although the study approach is similar to CAR-T cell therapy, Dr Stadtmauer said there are key differences. When a patient’s T cells are collected, instead of arming the cells with a receptor such as CD19, the team first uses CRISPR/Cas9 editing to remove three genes.

The first two edits remove immune receptors from the T cells to make sure they bind to the right part of the cancer cells. The third removes PD-1, a molecule involved in immune suppression. After that, a lentivirus is used to insert an affinity-enhanced T cell receptor (TCR), which tells the edited T cells to target the NY-ESO-1 antigen.

Senior study author Dr Carl June said its use of CRISPR editing aims to improve the effectiveness of gene therapies, rather than to edit a patient’s DNA.

The CRISPR-edited T cells require the presence of the HLA-A201 antigen, which is only expressed in a subset of patients. This meant patients had to be screened to make sure their tumours matched the study approach.

The three patients who met the requirements received other clinically indicated therapy as needed while they waited for their cells to be manufactured, after which they received the gene-edited cells in a single infusion after a short course of chemotherapy.

Analysis of blood samples demonstrated that the CRISPR-edited T cells expanded and survived in all three patients. None of them have yet responded to the treatment, although there were no serious adverse events. The researchers will continue to analyse patient samples so they have longer clinical follow-up to study this approach.

Dr Stadtmauer will present the findings on Saturday, December 7, at the 61st ASH Annual Meeting and Exposition in Orlando, FLA.

Source: University of Pennsylvania, https://www.pennmedicine.org/news/news-releases/2019/november/results-first-us-trial-crispr-edited-immune-cells-cancer-patients-safety-of-approach


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