1区 · 综合性期刊
Article
作者: Kim, Dongkyoon ; Nguyen, Ngan ; Kaplan, Hargita ; Robinson, William H. ; Wu, Dai-Chen ; Greenberg, Norman M. ; Zhang, Danhui ; Wechsler, Erin ; Czupalla, Cathrin J. ; Millward, Carl ; Benjamin, Jonathan ; Wu, Jenny W. ; Aydin, Iraz T. ; Harbell, Michael ; Whidden, Mark ; Leung, Yvonne ; Lippow, Shaun M. ; Vivian, John ; Ye, Anne Z. ; Baia, Gilson ; DeFalco, Jeff ; Steinman, Lawrence ; Peng, Xiao ; Santos, Daniel ; Scholz, Alexander ; Emerling, Daniel E. ; Collins, Rodney ; Vad, Nikhil ; Sapugay, Judevin ; Manning-Bog, Amy ; Cao, Wei ; Serafini, Tito A.
SignificanceA 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.