Mobilization of innate and adaptive antitumor immune responses by the RNP-targeting antibody ATRC-101

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.