Simone Krebs
Associate Professor
University of MD Anderson Cancer Center at Houston
Department of Nuclear Medicine and Imaging Physics
The primary focus of the Krebs Laboratory is the development and preclinical evaluation of imaging and theranostic agents including in conjunction with cellular engineering. Our bench-to-bedside research program includes chemistry, cellular biology, immunology, animal research, and clinical translation. For example, we are developing a non-invasive, safe, sensitive, and specific methodology to monitor genetically altered human immune cells, called chimeric antigen receptor (CAR) T cells, after they have been transferred into patients to treat cancer. We are also investigating theranostic approaches that target established and novel markers on the tumor and/or tumor microenvironment (TME) to i) elucidate the localization, dynamics, and underlying molecular pathways of immune-suppressive molecules in the TME; and ii) administer radioimmunotherapy. We are specifically investigating approaches to treat and diagnose glioma, lymphoma, and other selected tumors.
Interrogating the in vivo pharmacokinetics of armored CARs with radiohapten capture
Our goal is to develop a novel non-invasive, safe, sensitive, and specific methodology to monitor genetically altered human immune cells, called chimeric antigen receptor (CAR) T cells, after they have been transferred into patients to treat cancer. We have developed a DOTA antibody reporter, which binds to a clinically employed radiometal complex (DOTA) (1), and we propose to use this tool for tracking transfused CAR T cells to determine their location and study their functionality, and in case of imminent treatment failure, to exploit these engineered T cells to deliver a deadly payload to the tumor with the goal of improving the anti-tumor efficacy of CAR T-cell therapy. By combining next generation armored CAR T cells and molecular imaging and targeted radionuclide therapy, the proposed project has the potential to significantly endow these “living” drugs with novel attributes to increase their therapeutic potency and safety.
Novel human IL13Rα2-targeting antibodies for diagnosis and treatment of malignancies
Interleukin-13 receptor alpha-2 (IL13Rα2) is expressed with high frequency and specificity on some of the most aggressive and deadly cancers such as glioblastoma, basal-like triple-negative breast cancer, and melanoma. IL13Rα2 has limited expression in healthy tissue, rendering it an ideal target for noninvasive and specific tumor detection and treatment. Five novel human anti-IL13Rα2 antibodies (KLG-1–5) were developed. Lead candidate anti-IL13Rα2 antibody KLG-3 validated highly specific target binding in several tumor models, supporting further studies exploring its diagnostic and therapeutic potential following labeling with imaging or therapeutic radioisotopes.
Education & Training
MD, Albert-Ludwigs University of Freiburg, 2006