Michel Frank Ferrazo, Purchased Materials Technician at ABL Antibióticos do Brasil Ltda, shared a post on LinkedIn:
“14 of 16 B cell ALL samples carried surface U5 snRNP200.
AML CAR-T has a target problem: CD33, CD123 and CD371 can also appear on normal hematopoietic precursors or essential myeloid cells.
U5 snRNP200 is different in concept. It is an RNA helicase, usually nuclear, found on AML cell surfaces but not normal HSPCs.
The authors built CAR-T cells from graft versus leukemia antibodies isolated after allogeneic transplant remission, then armored the best construct with IL 18.
In B cell acute lymphoblastic leukemia, U5 snRNP200 was detected on 14 of 16 patient blast samples, ages 6 to 75.
In AML, IL 18 armored U5 snRNP200 CAR-T reduced leukemia in 3 adult PDX models and 1 pediatric PDX model.
The same CAR-T spared normal myeloid cells and T cells in vitro, and did not reduce colony formation from CD34 positive cord blood HSPCs.
The mechanism is not just target recognition. IL 18 increased IFN gamma, which raised CD32A and surface U5 snRNP200 on leukemia cells.
That creates a possible antigen gain loop, rather than the usual antigen loss problem seen after CD19 CAR-T.
Still preclinical, not final typeset. Xenograft deaths may include graft versus host disease, and normal B cell targeting remains expected.
Should AML CAR-T prioritize rare tumor selective targets like U5 snRNP200, or engineered shielding of common targets like CD33 and CD123?”
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