1区 · 综合性期刊
Article
作者: Ye, Anne Z. ; Czupalla, Cathrin J. ; Nguyen, Ngan ; Vivian, John ; Baia, Gilson ; Cao, Wei ; Lippow, Shaun M. ; Whidden, Mark ; Sapugay, Judevin ; Zhang, Danhui ; Peng, Xiao ; Collins, Rodney ; Millward, Carl ; Robinson, William H. ; Leung, Yvonne ; Serafini, Tito A. ; Wu, Jenny W. ; Greenberg, Norman M. ; Steinman, Lawrence ; Vad, Nikhil ; Wu, Dai-Chen ; Benjamin, Jonathan ; Scholz, Alexander ; Aydin, Iraz T. ; Manning-Bog, Amy ; Harbell, Michael ; Wechsler, Erin ; Emerling, Daniel E. ; Santos, Daniel ; Kim, Dongkyoon ; Kaplan, Hargita ; DeFalco, Jeff
Significance:A target-agnostic approach that harnesses the human antitumor immune response to find potential anticancer lead antibodies and their targets was used to generate ATRC-101, an engineered version of a tumor-targeting antibody identified from a patient with non-small cell lung cancer experiencing an ongoing antitumor immune response. ATRC-101 is an antibody that targets an extracellular, tumor-specific ribonucleoprotein complex. Here, we describe the extracellular binding of this complex and antitumor activity of ATRC-101 in murine models. Preclinical data suggest a mechanism of action in which ATRC-101 activates myeloid cells of the innate immune system, leading to an adaptive immune response that yields its antitumor activity. These data have led to an ongoing phase 1 trial in patients with advanced solid tumors.