CD7 gene-edited chimeric antigen receptor (CAR) T cells target CD7-positive acute myeloid leukemia (AML) cells while sparing myeloid and erythroid cells and minimizing toxicity, according to the results of a recent study.
CD7 gene-edited (CD7KO) chimeric antigen receptor (CAR) T cells can successfully target CD7-positive acute myeloid leukemia (AML) cells while sparing myeloid and erythroid cells and minimizing toxicity, according to the results of a recent study in Molecular Therapy.
Treatment of AML with CAR T has significantly improved response rates but has also been associated with toxicity against nonmalignant cells due to a lack of selective discrimination. CD7 is a glycoprotein expressed on approximately 30% of AML cells while also being absent on normal myeloid cells. A new study evaluated the efficacy of CD7 CAR T cells on AML in vitro and in vivo in mice.
Although normal myeloid cells did not express CD7, regular T cells did. To retain functionality, the CD7 gene of T cells was edited prior to CD7 CAR expression (CD7KO). When examining the different cell types, investigators found that CD7 was not expressed in peripheral monocytes, granulocytes, or B cells; however, natural killer and T cells did express CD7. When AML cells were collected, they also showed CD7 expression in 6 of the 20 samples, consistent with previous findings.
To analyze the efficacy of CD7 CAR T cells, investigators cultured CD7-positive AML cells with T cells expressing CD7 and incubated them for 3 to 5 days. In an effector-to-target ratio of 1:40, there was a 2 to 3 log reduction in the counts of malignant cells. Furthermore, cytotoxicity was observed in effector-to-target ratios ranging from 1:4 to 1:50, demonstrating high cytotoxicity potential. CD7-expressing T cells were not only highly cytotoxic, but also maintained robust and sustained cytotoxicity. Even after the introduction of 6 rounds of fresh tumor cells, CD7-expressing T cells still exerted activity.
In vivo tests in mice also demonstrated positive eradication of AML cells. Mice with AML that were administrated nontransduced T cells developed systemic leukemia and died with a median survival of 54 days. In comparison, mice that received CD7 CAR T cells reversed leukemia progression and had no observed tumor growth for the 125 days of the experiment.
This study helped demonstrate that CD7 CAR T cells are an effective treatment option for AML. Because CD7 is not present on myeloid and erythroid cells, there is less risk of toxicity to these normal cells. Future tests will need to be done in humans to determine the efficacy, safety, and potential use of CD7 CAR T cells.
Golmes-Silva D, Atilla E, Atilla PA, et al. CD7 CAR T cells for the therapy of acute myeloid leukemia [published online October 4, 2018]. Mol Ther. doi: 10.1016/j.ymthe.2018.10.001.