Tim-Mathis Beutel

Md Candidate @Cecad Cologne

Cologne, DE

In the group of Walczak et al. demonstrated for the first time that TRAIL can be used safely in vivo and induces apoptosis of cancer cells while not harming healthy cells, whereas FasL is highly toxic when used in the same way. This good tolerability and its selectivity made TRAIL a promising candidate for cancer therapy. However, clinical trials with dulanermin (AMG951), a non-tagged zinc-coordinated soluble homotrimeric c-terminal recombinant TRAIL, failed. TNF and FasL are known to be released from the plasma membrane by metalloproteinase-mediated cleavage by ADAM17 and ADAM10, respectively. Although soluble TRAIL can be detected at a concentration of 100 pg/mL in the plasma of a healthy adult, the cleaving protease has not yet been deciphered. It is known that only the membrane-bound FasL, but not its soluble cytokine, can induce apoptosis. Considering the similarities in the downstream signaling pathways of TRAIL and FasL, this may explain the clinical failure of dulanermin. Therefore, the cleavage of TRAIL needs to be elucidated.

Max-Planck-Gymnasium Dortmund

Abitur

Universität zu Köln

Staatsexamen

Boston University School of Medicine

Clinical rotation

Ludwig-Maximilians-Universität München

Staatsexamen, Humanmedizin

Westphalian Institute of Health Care Professionals

Professional education