Blood Podcast Novel Treatment Targets for Hemophilia A and AML
Dec 25, 2025
Join researcher Vincent Muczynski, who presents a groundbreaking AAV gene therapy strategy for hemophilia A using a novel bispecific antibody. He details impressive preclinical results showing promise in correcting bleeding in mice. Clinician-scientist Mark Geyer unveils his phase 1 study on CD371-targeted CAR T cells infused with interleukin-18, which shows potential in tackling relapsed/refractory acute myeloid leukemia. Translational scientist Susan DeWolf shares insights from their analyses, revealing how interleukin-18 fosters immune remodeling and enhances treatment effectiveness.
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Small Bi8 Solves AAV Size Constraint
- AAV capsid size limits make delivering full FVIII impractical for gene therapy.
- Converting a bispecific FVIII-mimetic into a 1.5 kb single-chain (Bi8) bypasses that constraint and preserves function.
Bi8 AAV8 Shows Durable Functional Rescue
- AAV8 liver-directed delivery of Bi8 produced stable, dose-dependent expression in hemophilia A mice for at least eight weeks.
- Treated mice showed near-normal bleeding outcomes comparable to emicizumab or recombinant FVIII.
Extend Bi8 Half-Life To Lower Doses
- Improve Bi8 pharmacokinetics by adding an albumin-binding moiety to extend half-life.
- Extended half-life should lower required vector dose and improve gene therapy safety and durability.