Targeting CD7 to treat T-cell acute lymphoblastic leukemia
A novel CAR-T cell therapy targeting CD7 has proven effective in treating relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL).
In a recently published case series, researchers from the Yong Loo Lin School of Medicine, National University of Singapore, National University Health System (all Singapore) and Ospedale Pediatrico Bambino Gesù (Rome, Italy) detail the success of a new type of CD7-targeted CAR-T cell therapy in patients with T-ALL.
T-ALL is a typically aggressive blood cancer and is particularly difficult to treat in patients who have experienced relapse following treatment or whose cancer is chemoresistant. To tackle such cases, the Singapore-based research team developed a novel CAR-T cell therapy targeting the CD7 protein, which is highly expressed in leukemia T cells. Like other CAR-T therapeutics, these cells are manufactured by harvesting patients’ T cells and reprogramming them to express a CAR on their cell surface – in this case, an anti-CD7 CAR. Upon reinfusion into the patent, these anti-DC& CAR-T cells recognize and destroy cancerous cells expressing CD7.
However, the CD7 protein is also expressed by some healthy cells, including the CAR-T cells themselves. To prevent the engineered cells from recognizing and destroying one another – a process termed fratricide – the researchers also added a protein expression blocker to stop CD7 from being expressed on the CAR-T cell surface. This prevents fratricide by essentially concealing the engineered cells from one another, so they are not recognized and killed.
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The research team tested the treatment in 17 patients at institutions in Singapore and Italy with T-ALL that had relapsed or could not be eliminated with chemotherapy. The treatment was safe and well tolerated with relatively mild side effects. Remarkably, 16 of the treated patients achieved complete remission within a month, with their disease deemed undetectable even by highly sensitive screening techniques. Furthermore, the first participant in the study remains in remission for over 55 months after initially receiving treatment, without needing any additional chemotherapy or a stem cell transplant.
“While we celebrate this wonderful milestone, we are only at the beginning of this exciting journey. There is a lot of scientific and medical enquiry to understand how to better use CD7 CAR-T cells,” explained researcher Allen Yeo (National University of Singapore), who led the treatment’s clinical application. “Each patient in this series taught us a lot. Ultimately, for every member of our team, seeing each patient smile and given another chance after achieving remission is priceless.”