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- W3137393431 abstract "Alternative strategies are needed for patients with B-cell malignancy relapsing after CD19-targeted immunotherapy. Here, cell surface proteomics revealed CD72 as an optimal target for poor-prognosis KMT2A/MLL1-rearranged (MLLr) B-cell acute lymphoblastic leukemia (B-ALL), which we further found to be expressed in other B-cell malignancies. Using a recently described, fully in vitro system, we selected synthetic CD72-specific nanobodies, incorporated them into chimeric antigen receptors (CAR), and demonstrated robust activity against B-cell malignancy models, including CD19 loss. Taking advantage of the role of CD72 in inhibiting B-cell receptor signaling, we found that SHIP1 inhibition increased CD72 surface density. We establish that CD72-nanobody CAR-T cells are a promising therapy for MLLr B-ALL. SIGNIFICANCE: Patients with MLLr B-ALL have poor prognoses despite recent immunotherapy advances. Here, surface proteomics identifies CD72 as being enriched on MLLr B-ALL but also widely expressed across B-cell cancers. We show that a recently described, fully in vitro nanobody platform generates binders highly active in CAR-T cells and demonstrate its broad applicability for immunotherapy development.This article is highlighted in the In This Issue feature, p. 1861." @default.
- W3137393431 created "2021-03-29" @default.
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- W3137393431 date "2021-05-16" @default.
- W3137393431 modified "2023-10-12" @default.
- W3137393431 title "Surface Proteomics Reveals CD72 as a Target for <i>In Vitro</i>–Evolved Nanobody-Based CAR-T Cells in <i>KMT2A/MLL1</i>-Rearranged B-ALL" @default.
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- W3137393431 doi "https://doi.org/10.1158/2159-8290.cd-20-0242" @default.
- W3137393431 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8338785" @default.
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