Potent Apoptosis Induction by a Novel Trispecific B7-H3xCD16xTIGIT 2+1 Common Light Chain Natural Killer Cell Engager.
Michael UlitzkaJulia HarwardtBritta LipinskiHue TranBjörn HockHarald KolmarPublished in: Molecules (Basel, Switzerland) (2024)
Valued for their ability to rapidly kill multiple tumor cells in succession as well as their favorable safety profile, NK cells are of increasing interest in the field of immunotherapy. As their cytotoxic activity is controlled by a complex network of activating and inhibiting receptors, they offer a wide range of possible antigens to modulate their function by antibodies. In this work, we utilized our established common light chain (cLC)-based yeast surface display (YSD) screening procedure to isolate novel B7-H3 and TIGIT binding monoclonal antibodies. The chicken-derived antibodies showed single- to low-double-digit nanomolar affinities and were combined with a previously published CD16-binding Fab in a 2+1 format to generate a potent NK engaging molecule. In a straightforward, easily adjustable apoptosis assay, the construct B7-H3xCD16xTIGIT showed potent apoptosis induction in cancer cells. These results showcase the potential of the TIGIT NK checkpoint in combination with activating receptors to achieve increased cytotoxic activity.
Keyphrases
- nk cells
- endoplasmic reticulum stress
- cell cycle arrest
- oxidative stress
- signaling pathway
- cell death
- anti inflammatory
- dna damage
- pi k akt
- single cell
- microbial community
- dna binding
- high throughput
- randomized controlled trial
- minimally invasive
- cell therapy
- systematic review
- stem cells
- saccharomyces cerevisiae
- network analysis