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Biotechnology

CRISPR’d T cells for use in immunotherapy deemed safe in human trial

Scientists used the gene-editing technique to modify 3 genes in the human cells to target them to cancer cells

by Megha Satyanarayana
February 6, 2020 | APPEARED IN VOLUME 98, ISSUE 6

 

A team of scientists has found that T cells from people with cancer can be removed, modified using the CRISPR gene-editing technique, and safely returned to the patients, setting the stage for subsequent cancer immunotherapy trials using the popular gene-editing technique (Science 2020, DOI: 10.1126/science.aba7365).

The trial, led by Carl June of the University of Pennsylvania, involved three people, two with advanced myeloma and one with metastatic sarcoma. The research team removed T cells from each person and made three gene changes with CRISPR. They removed the genes for the α and β subunits of the T-cell receptor and then engineered the cells to display a different, cancer-specific receptor. In immunotherapy, such cell surface proteins engage with molecules on cancer cells, beginning the immune attack that leads to a cancer cell’s death. A third edit removed the gene encoding PD-1, a checkpoint protein that tamps down immune response.

The three people had no strong immune response to Cas9, the bacterial protein that initiates DNA cutting in CRISPR, and they did not experience excessive cytokine release, a common side effect in early trials of cell-based immunotherapy. The engineered T cells persisted in the patients for weeks longer than those in other trials who received T cells with PD-1. The Phase I trial did not test tumor-killing efficacy.

Prasad Adusumilli, a cell therapy expert at Memorial Sloan Kettering Cancer Center, says the initial results are exciting and that future tests will hopefully address both the feasibility of doing this on a large number of patients and the consistency of the gene editing.

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