ArticleImmunotherapy2025
CD33-D2 isoform characterization for advancement of its therapeutic potential.
Article in Immunotherapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
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4 authors.
Funding
Abstract
purposeWhile CD33 directed immunotherapies have caught significant interest in recent years, the only approved antibody-drug conjugate targeting this antigen for AML is gemtuzumab ozogamicin, which targets the IgV-domain of CD33. Unfortunately, in its current form, these are not effective in a significant proportion of patients due to the presence of a splicing SNP resulting in the loss of IgV-domain. This, however, can be mitigated by targeting the IgC2-domain of CD33; thus, this study aimed to characterize CD33-D2 isoform using the recently developed CD33-D2-targeting antibody HL2541.
methodsGenetically engineered AML cell lines expressing CD33 isoforms were tested for antibody-bound internalization and response to GO
resultsHL2541-bound-CD33-D2 is internalized similar to CD33-FL upon binding the antibody component of GO. Co-existence of both isoforms compromises the internalization by >2.5-3-fold for each isoform in the AML cell lines, further resulting in 7-9.5-fold higher IC
conclusionThe results establish the relevance of targeting IgC domain as an alternative immunotarget to supplement AML chemotherapy.
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