Cancers, Vol. 12, Pages 2659: NK-Cell-Mediated Targeting of Various Solid Tumors Using a B7-H3 Tri-Specific Killer Engager In Vitro and In Vivo

Cancers, Vol. 12, Pages 2659: NK-Cell-Mediated Targeting of Various Solid Tumors Using a B7-H3 Tri-Specific Killer Engager In Vitro and In Vivo Cancers doi: 10.3390/cancers12092659 Authors: Daniel A. Vallera Soldano Ferrone Behiye Kodal Peter Hinderlie Laura Bendzick Brianna Ettestad Caroline Hallstrom Nicholas A. Zorko Arpit Rao Naomi Fujioka Charles J. Ryan Melissa A. Geller Jeffrey S. Miller Martin Felices We improved the bispecific antibody platform that primarily engages natural killer (NK) cells to kill cancer cells through antibody-dependent cellular cytotoxicity (ADCC) by adding IL-15 as a crosslinker that expands and self-sustains the effector NK cell population. The overall goal was to target B7-H3, an established marker predominantly expressed on cancer cells and minimally expressed on normal cells, and prove that it could target cancer cells in vitro and inhibit tumor growth in vivo. The tri-specific killer engager (TriKETM) was assembled by DNA shuffling and ligation using DNA encoding a camelid anti-CD16 antibody fragment, a wild-type IL-15 moiety, and an anti-B7-H3 scFv (clone 376.96). The expressed and purified cam1615B7H3 protein was tested for in vitro NK cell activity against a variety of tumors and in vivo against a tagged human MA-148 ovarian cancer cell line grafted in NSG mice. cam1615B7H3 showed specific NK cell expansion, high killing activity across a range of B7-H3+ carcinomas, and the ability to mediate growth inhi...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research