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- W4313355958 abstract "Abstract While treatment of chronic lymphocytic leukemia (CLL) has been advanced by introduction of targeted therapies such as tyrosine kinase inhibitors, there remains a need for adjunct therapies capable of inducing response in the setting of relapse on or resistance to first-line agents. Blinatumomab is a bispecific antibody (bsAb) against CD19/CD3, designed to target endogenous T cells against B cells via the formation of cytolytic synapses. It is approved for treatment of relapsed/refractory B-cell acute lymphoblastic leukemia, and has shown promise for use in non-Hodgkin’s lymphoma. Designed in the relatively small 54.1 kDa BiTE format, blinatumomab has a half-life of 2.1 hours and requires continuous intravenous infusion for clinical efficacy. In contrast, our novel anti-CD19/CD3 bsAb, designed in the 100 kDa single chain Fv-Fc format (CD19/CD3-scFv-Fc), has an approximately 100-fold longer half-life and could therefore be suitable for weekly dosing. We found that both blinatumomab and CD19/CD3-scFv-Fc induce potent killing of CLL cells ex vivo compared to cells treated with control HER2/CD3-scFv-Fc bsAb or medium alone. This response was associated with robust expansion of autologous CD4+ and CD8+ T cells, as shown by absolute cell counts and CFSE-detected population doubling. Notably, while HER2/CD3-scFv-Fc induced T cell expansion, no CLL directed cytotoxicity was observed. Our results identify CD19/CD3-scFv-Fc as a possible novel immune-based treatment for CLL." @default.
- W4313355958 created "2023-01-06" @default.
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- W4313355958 date "2017-05-01" @default.
- W4313355958 modified "2023-09-27" @default.
- W4313355958 title "CD19/CD3 bispecific antibodies induce potent response against chronic lymphocytic leukemia cells <i>ex vivo</i>" @default.
- W4313355958 doi "https://doi.org/10.4049/jimmunol.198.supp.120.17" @default.
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