On January 15, 2018 LeadArtis´scientists, in collaboration with other prime research institutions, reported a new tactic to generate multispecific T-cell recruiting antibodies to eradicate cancers (Press release, LeadArtis, JAN 15, 2018, View Source [SID1234523122]).
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The redirection of T cell activity using bispecific antibodies is one of the most promising cancer immunotherapy approaches currently in development, but it is limited by cytokine storm-related toxicities, as well as the pharmacokinetics and tumor-penetrating capabilities of current bispecific antibody formats. We have engineered the ATTACK (Asymmetric Tandem Trimerbody for T cell Activation and Cancer Killing), a novel T cell-recruiting bispecific antibody which combines three Tumor Associated Antigen (TAA) binding single-domain antibodies with a single CD3-binding domain in an intermediate molecular weight package. The two specificities are oriented in opposite directions in order to simultaneously engage cancer cells and T cell effectors, and thereby promote immunological synapse formation. The ATTACK molecules are expressed as homogenous, non-aggregating, soluble proteins by mammalian cells and demonstrated an enhanced binding to the TAA but not CD3. The ATTACKs demonstrated extremely potent, dose-dependent cytotoxicity when retargeting human T cells towards TAA-expressing cells. These results suggest that the ATTACK is an ideal format for the development of the next-generation of T cell-redirecting bispecific antibodies.
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