Article
作者: Rogers, Katharine ; Patel, Jaymala ; Schutsky, Keith ; Shenton, Jacintha ; Hamuro, Yoshitomo ; Yi, Fang ; Tian, Ken ; Zwolak, Adam ; Jarantow, Stephen ; Angelillo, Lorraine ; Obermajer, Nataša ; Aligo, Jason ; Petley, Ted ; Versmissen, Shana ; Brajic, Aleksandra ; Lorenzi, Matthew V ; Greger, James G ; Laquerre, Sylvie ; Lauring, Josh ; Brehmer, Dirk ; Verbist, Bie ; Singh, Sanjaya ; Menard, Krista ; Weinstock, Dan ; van Heerden, Marjolein ; Ongenaert, Maté ; Torti, Vince ; Chu, Gerald ; van de Ven, Kelly ; Häsler, Julien ; Brown, Regina J ; Buyens, Kristel ; Arias, Diana Alvarez ; Packman, Kathryn ; Lenox, Laurie ; Geist, Brian ; Clawson, Jacalyn ; Sheena Yao, Tsun-Wen
T cell-redirecting bispecific antibodies (bsAbs) to treat advanced stage solid tumors are gaining interest after recent clinical successes. The immune checkpoint human leukocyte antigen G (HLA-G) is expressed in several tumor types while in normal tissues expression is limited. Here, we describe JNJ-78306358, a T cell-redirecting bispecific antibody (bsAb) to treat advanced stage solid tumors. JNJ-78306358 binds with high affinity to the α3 subunit of HLA-G on cancer cells and with purposely engineered weaker affinity to CD3ε on T cells. JNJ-78306358 induced potent T cell-mediated cytotoxicity of HLA-G-expressing solid tumors in vitro and in vivo. JNJ-78306358 also blocked the interaction of HLA-G with its receptors in vitro, indicating that immune checkpoint blocking may contribute to its anti-tumor activity. These results suggest that T cell-redirection against HLA-G could be a potent and effective treatment for a wide range of solid tumor indications.