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Natural killer (NK) cells are cytotoxic lymphocytes of the innate immune system capable of broad cytotoxicity and immune surveillance via the addition of chimeric antigen receptors. Combined with their reduced risk of graft-versus-host disease (GvHD) and cytokine release syndrome (CRS), NK cells are an attractive therapeutic platform. However, the effectiveness of NK cell infusions to induce hematological malignancies remission is limited by the lack of both antigen specificity and in vivo expansion in tumor microenvironments (TMEs).
To overcome these limitations, Creative Biolabs has developed an antibody-based molecule, Tri specific Natural Killer Engagers (TriKEs), that have been designed to improve NK cell anti-tumor activity. The TriKEs system creates an immunological synapse between a tumor cell and NK cell promoting the release of cytotoxic granules and exhibits the potential to expand treatment options for hematologic and solid tumors, both as monotherapy and in combination with other agents or adoptive NK cell transfer.
TriKEs typically comprise two monoclonal antibody fragments, one specific to endogenous CD16 on NK cells, and the other specific to a tumor-associated antigen, connected by a linker, and also include a stimulatory cytokine such as IL-15 or IL-21 meant to improve NK expansion, viability, and function within a TME. The TriKEs system not only promotes NK cell expansion, NK cell cytotoxicity against tumor via CD16 activation but also improves NK cell survival and proliferation capacity to overcome the TME. Additionally, TriKEs can also be adapted to target antigens expressed on solid tumors.
Fig.1 Design and function of TriKEs.
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CellRapeutics™ In Vivo Cell Engineering: One-stop in vivo T/B/NK cell and macrophage engineering services covering vectors construction to function verification.
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