Abstract NT-099: NOVEL ANTIBODY DRUG CONJUGATE (ADC) AND COMPANION DIAGNOSTICS AGAINST CD248+ CANCER

Abstract

Antibodies recognizing specific tumor targets can be used to deliver therapeutic payloads with high degree of specificity. The simultaneous use of antibody against same target for imaging and for therapy, an approach named “theranostics”, offers unique opportunities for precision medicine and rapidly assessing therapeutic response at molecular level. The first example of such antibody-based theranotics is Herceptin in HER2-positive breast cancer: Herceptin is used as companion diagnostic imaging tool as well as the targeted therapy. To develop effective anti-tumor therapeutics, one needs a robust biomarker, AND a good antibody that can specifically bind to the target. We and others have found one for EOC: CD248/TEM1. It is present at high level in tumor and its microenvironment in EOC and almost absent in normal organs. Importantly, CD248 is expressed by >90% EOC patients on the tumor or tumor vasculature, and its high expression correlates with poor survival. This means that if we can target it, we may destroy tumor but leave normal tissues intact. We also have developed robust antibody against CD248 (78Fc panel, US Patent 61/639,325). We showed that our patented antibodies can find the biomarker and upon binding deliver a payload, for PET imaging, near-infrared optical imaging or therapeutic, to CD248-expressing cells. Different toxin payload, such as auristatin and MD117, were conjugated to the antibody, and such ADCs were tested in vitro and in vivo in mice models. Surprisingly, we found such immunotherapies only directly kill, but also induce significant lymphocyte infiltration into tumors. In addition, tumor rejection was observed upon re-challenging in preclinical models. Such immune activation we observed could in turn sensitizing previously “cold tumor” EOC, to checkpoint inhibitors such as PD-1/CDLA4. The long term goal is to develop companion diagnostics and antibody-immunotherapy: screening methods (such as antibody-based immunoPET and serum ELISA) to identify patients with EOC that can be treated with anti-CD248 drugs; and develop drugs that are linked to the antibody (such as antibody-drug conjugate) so it can be delivered to the tumor directly to kill. In addition, combined with PD-1 blockade, ADC therapies may exert antitumor immune response to sensitize “cold” tumors that previously resistant to PD-1 therapy. Citation Format: Yi Guo, Yujue Wang, Xiaohui Peng, George Coukos, Chunsheng Li. NOVEL ANTIBODY DRUG CONJUGATE (ADC) AND COMPANION DIAGNOSTICS AGAINST CD248+ CANCER [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr NT-099.