Among patients with CD70-positive acute myeloid leukemia (AML), CD-70 targeting chimeric antigen receptor (CAR) T-cell therapy may be a promising therapeutic strategy, according to a cell line-based study published in Blood.
AML is the most commonly diagnosed leukemia subtype among adults. Although treatment options have improved over the past several decades, more than half of patients who reach remission after intensive chemotherapy are likely to relapse.
Previous research suggested that the high rates of remission in AML are due to leukemic stem cells, which are resistant to chemotherapy. Research suggests, furthermore, that eliminating leukemic stem cells is essential for curative treatment.
CAR-T cell therapy has shown promise in other hematologic malignancies, particularly those expressing CD-19. CD70, a type 2 transmembrane glycoprotein and tumor necrosis factor family member, is expressed on both leukemic blasts and leukemic stem cells. CAR-T therapy targeting CD70 could, furthermore, act on AML cells without affecting hematopoiesis.
For this cell line study, researchers evaluated the effectiveness of targeting CD70 with CAR-T cell therapy in AML. The researchers designed a panel of CAR-T cells targeting CD70 to determine their relative efficacy at eliminating target cells while sparing normal hematopoietic stem cells. The designed panel contained a single-chain variable fragment to detect antigens, though differed in other reported domains.
The researchers compared the panel of designed cells with CAR constructs containing CD27, CD70’s ligand fused to the CD3z chain (CD27z). Analysis suggested that, in the single-chain variable fragment-containing panel, CAR composition affected expression levels, viability, expansion, and cytotoxic capabilities. CD27z-cells, however, showed improved proliferation and anti-cancer activity in vitro and in vivo.
CD70-CAR T cells did not, furthermore, prevent normal hematopoietic stem cell colony formation.
“In summary, CD70 is a promising target antigen for CAR T-cell therapy for AML,” the authors wrote. “We designed a panel of CD70 CAR T cells, and T cells expressing CAR T cells based on the CD70 receptor (CD27z-CAR T cells) emerged as the most beneficial CAR T-cell product, as shown by their anti-AML activity and ability to expand and persist.”
Disclosure: The study author(s) declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Reference
Sauer T, Parikh K, Sharma S, et al. CD70-specific CAR T cells have potent activity against acute myeloid leukemia without HSC toxicity. Blood. 2021;138(4):318-30. doi:10.1182/blood.2020008221