Article
作者: Häsler, Julien ; Laquerre, Sylvie ; van Heerden, Marjolein ; Obermajer, Nataša ; Brehmer, Dirk ; Clawson, Jacalyn ; Packman, Kathryn ; Hamuro, Yoshitomo ; Brown, Regina J ; Torti, Vince ; Greger, James G ; Verbist, Bie ; Lenox, Laurie ; Arias, Diana Alvarez ; Rogers, Katharine ; Buyens, Kristel ; Versmissen, Shana ; Sheena Yao, Tsun-Wen ; Jarantow, Stephen ; Tian, Ken ; Schutsky, Keith ; Zwolak, Adam ; Chu, Gerald ; Aligo, Jason ; Geist, Brian ; Ongenaert, Maté ; Shenton, Jacintha ; van de Ven, Kelly ; Lauring, Josh ; Angelillo, Lorraine ; Weinstock, Dan ; Patel, Jaymala ; Brajic, Aleksandra ; Petley, Ted ; Menard, Krista ; Lorenzi, Matthew V ; Yi, Fang ; Singh, Sanjaya
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.