Double Agents

CRISPR technology has caused cancer cells to destroy the tumor

Natalia Pelezneva, Naked Science

Scientists from Harvard Medical School have developed a technique that allows to influence neoplasms with the help of genetically modified circulating tumor cells. The technology was tested on laboratory mice. The study was published in the journal Science Translational Medicine (Reinshagen et al., CRISPR-enhanced engineering of therapy-sensitive cancer cells for self-targeting of primary and metastatic tumors).

Circulating tumor cells are separated from the neoplasm that originally appeared in the body and enter the bloodstream, and subsequently can return to the tumor. These cells are associated with the appearance of metastases – distant secondary foci of the disease. Such cells have already been used in cancer therapy (for example, to deliver certain substances to a tumor), but their CRISPR modification has been investigated relatively recently.

As a weapon against tumors, the authors of the new work used the S-TRAIL protein, capable of provoking apoptosis – programmed cell death. The researchers tested several compounds that cause cell death, and S-TRAIL turned out to be the least toxic to healthy body cells.

The scientists then tried two approaches to circulating cell therapy. In the first case, they used glioblastoma cells – an aggressive brain tumor – resistant to the effects of S-TRAIL. Modification using CRISPR technology forced these cells to actively produce a killer protein, then they were injected into the body of experimental mice with primary tumors. In this approach, allogeneic (foreign) cells are used – taken from another organism or obtained artificially – therefore, during therapy with this method, cells compatible with the phenotype of the patient's HLA antigens will have to be specially selected.

The second method was used for mice with recurrent tumors. From the tissue of their primary neoplasms, scientists obtained cells sensitive to S-TRAIL, and first "turned off" the receptors responsible for this susceptibility by genetic engineering methods so that the cells would not destroy themselves prematurely. After that, the prepared cells were also forced to produce S-TRAIL and injected into the animals. A "switch" was built into both types of cells, triggering the process of self-destruction of killer cells at the end of treatment.

Two methods of therapy
© Science Translational Medicine

According to scientists, both approaches were effective. The tests involved mice with primary and re-developed brain tumors, as well as breast tumors whose metastases penetrated into the brain: scientists managed to reduce the size of neoplasms of all types. Also, mice that underwent such therapy lived longer.

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