2018 Early Career Investigator Grant Recipient — Chunsheng Li, PhD
Project Summary
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 vascular 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 imaging or therapeutic, to CD248-expressing cells. 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 (in submission). Such immune activation we observed could in turn sensitizing previously “cold tumor” EOC, to checkpoint inhibitors such as PD-1/CDLA4.
This project intends to develop companion diagnostics and antibody-immunotherapy with this antibody: screening methods (such as antibody-based immunoPET and serum ELISA) to identify patients with EOC that can be treated with anti-CD248 drugs; we will then 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, how ADC therapies exert antitumor immune response to sensitize “cold” tumors that previously resistant to PD-1 therapy.