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A bispecific nanobody approach to leverage the potent and widely applicable tumor cytolytic capacity of V?9V?2-T cells.


ABSTRACT: Though V?9V?2-T cells constitute only a small fraction of the total T cell population in human peripheral blood, they play a vital role in tumor defense and are therefore of major interest to explore for cancer immunotherapy. V?9V?2-T cell-based cancer immunotherapeutic approaches developed so far have been generally well tolerated and were able to induce significant clinical responses. However, overall results were inconsistent, possibly due to the fact that these strategies induced systemic activation of V?9V?2-T cells without preferential accumulation and targeted activation in the tumor. Here we show that a novel bispecific nanobody-based construct targeting both V?9V?2-T cells and EGFR induced potent V?9V?2-T cell activation and subsequent tumor cell lysis both in vitro and in an in vivo mouse xenograft model. Tumor cell lysis was independent of KRAS and BRAF tumor mutation status and common V?9V?2-T cell receptor sequence variations. In combination with the conserved monomorphic nature of the V?9V?2-TCR and the facile replacement of the tumor-specific nanobody, this immunotherapeutic approach can be applied to a large group of cancer patients.

SUBMITTER: de Bruin RCG 

PROVIDER: S-EPMC5739573 | BioStudies | 2017-01-01T00:00:00Z

SECONDARY ACCESSION(S): 7D12

REPOSITORIES: biostudies

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