Potent Apoptosis Induction by a Novel Trispecific B7-H3xCD16xTIGIT 2+1 Common Light Chain Natural Killer Cell Engager

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...

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Bibliographic Details
Published inMolecules (Basel, Switzerland) Vol. 29; no. 5; p. 1140
Main Authors Ulitzka, Michael, Harwardt, Julia, Lipinski, Britta, Tran, Hue, Hock, Björn, Kolmar, Harald
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 01.03.2024
MDPI
Subjects
Antibodies
Antibodies, Monoclonal
Antigens
Apoptosis
bispecific antibody
Cells
checkpoint inhibitor
chicken-derived
Cytokines
Cytotoxicity
Immunotherapy
Killer cells
Killer Cells, Natural
Libraries
NK cell engager
Proteins
Receptors, Immunologic
Scientific equipment and supplies industry
trispecific antibody
Yeast
United States
Germany
NK cell engager
common light chain
chicken-derived
immunotherapy
bispecific antibody
trispecific antibody
apoptosis
yeast surface display
checkpoint inhibitor
monoclonal antibodies
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Summary: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.
Bibliography:ObjectType-Article-1
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ISSN:1420-3049
1420-3049
DOI:10.3390/molecules29051140