An off-the-shelf, gene edited CAR T-cell therapy, developed by the French biotech Cellectis, could be used to tackle solid tumors, which have so far been beyond the reach of other CAR T-cell therapies.
The approved CAR T-cell therapies Kymriah and Yescarta contain genetically modified immune T-cells that can fight certain types of blood cancer. However, these therapies are unable to tackle solid tumors because the tumors can suppress many types of immune cells in their vicinity. Cellectis’ preclinical CAR T-cell therapy is designed to overcome this barrier by releasing an inflammatory protein called IL-12 that helps the cells resist the tumor’s suppressive effects.
Cellectis established a preclinical proof-of-concept for its new CAR T therapy in a study published in Nature Communications. According to the study, the cell therapy significantly boosted the survival of seven mice with tumors compared to four mice that were left untreated.
Cellectis’ therapy is also designed to overcome another hurdle of current therapies. Currently, T-cells for each therapy are taken from the patients before being modified, involving a complex and costly chain of transport and manufacture. Instead of being derived from the patients’ cells, Cellectis’ therapy is designed to be off-the-shelf, letting the company stockpile cells from donors ready to be used when needed.
Other companies have played with the idea of making CAR T-cells release inflammatory proteins such as the US company Juno Therapeutics, now owned by Celgene. However, these proteins can also cause damage to healthy tissue if uncontrolled, resulting in serious side effects. To get around this, Cellectis’ cells are designed to produce them only when in contact with the tumor, which should make the therapy safer.
Cellectis isn’t the only company working on off-the-shelf CAR T-cell therapies for solid tumors. The Belgian biotech Celyad recently published the first-ever clinical results for a CAR T-cell therapy in patients with colorectal cancer. Celyad’s treatment is designed to attack solid tumors by genetically modifying T-cells with proteins that resemble those from tumor-hunting immune cells called natural killer cells.
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