Alicja Copik’s Post

I am excited to share our recent publication demonstrating that Fc-active anti-TIGIT therapeutics can deplete NK cells via fratricide. Therapies targeting TIGIT have so far underperformed in clinics, particularly anti-TIGIT that can engage antibody-dependent cell cytotoxicity (Fc-active). NK cells are a critical population for the efficacy of anti-TIGIT therapeutics, and our prior work demonstrated that activated NK cells overexpress TIGIT, correlating with better anti-tumor function (https://lnkd.in/ewr3TJsn).  Therefore, the depletion of NK cells by Fc-active anti-TIGIT candidates may contribute to their failure. Here, we showed that knocking out TIGIT prevents fratricide, enhances NK cell cytotoxicity, and improves their metabolism. Thus, co-administration with TIGIT KO NK cells may offer a potential solution to improve the effectiveness of anti-TIGIT therapies.  This work was led by a talented graduate student in my laboratory Md Faqrul Hasan and a postdoctoral fellow Tayler Croom-Perez.  I am also grateful for the wonderful collaboration and contributions of my long-time collaborator, Dr. Dean Lee, and his group. Well done, team! #TIGIT, #NK cells, #immunotherapy