Targeting the membrane-proximal C2-set domain of CD33 for improved CD33-directed immunotherapy.

ABSTRACT: There is increasing interest in targeting CD33 in malignant and non-malignant disorders. In acute myeloid leukemia, longer survival with the CD33 antibody-drug conjugate gemtuzumab ozogamicin (GO) validates this strategy. Still, GO benefits only some patients, prompting efforts to develop more potent CD33-directed therapeutics. As one limitation, CD33 antibodies typically recognize the membrane-distal V-set domain. Using various artificial CD33 proteins, in which this domain was differentially positioned within the extracellular portion of the molecule, we tested whether targeting membrane-proximal epitopes enhances the effector functions of CD33 antibody-based therapeutics. Consistent with this idea, a CD33^V-set/CD3 bispecific antibody (BsAb) and CD33^V-set-directed c

SUBMITTER: Godwin CD 

PROVIDER: S-EPMC8364569 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature