BPS 2018
Tumor penetrating peptides: discovery and clinical development
Tambet Teesalu
Professor, University of Tartu, Estonia
ABSTRACT
Our laboratory uses in vivo phage display to identify homing peptides that bind to specific targets in the vasculature. Corresponding synthetic peptides are used to target drugs, biologicals, and nanoparticles into tumors to increase their therapeutic index. Our scope includes understanding the molecular interactions involved to drive specificity and activity, focusing on tumor penetrating peptides that trigger bulk extravascular transport in the tumor tissue.
I will discuss our approaches to mapping of vascular heterogeneity using in vivo peptide phage display, characterization and validation of candidate vascular homing peptides, and application of the peptides for precision guided delivery of therapeutic and diagnostic compounds and nanocarriers.
I will discuss preclinical and clinical development of the prototypic tumor penetrating peptide, iRGD (Cend-1, developed by www.drugcendr.com) as an adjuvant to increase extravasation and accumulation of anticancer drugs in solid tumors for increased potency and less side effects.
BIO
Prof. Tambet Teesalu works on affinity targeting of tumors with homing peptides and peptidomimetic compounds. Since 2012, he heads the Laboratory of Cancer Biology at the University of Tartu, Estonia (www.cancerbiology.ee). The laboratory uses phage display screens to identify homing peptides that bind to specific targets in the tumor vasculature. Corresponding synthetic peptides are developed for targeting drugs, biologicals, and nanoparticles into tumors to increase their therapeutic index.
Prof. Teesalu received his PhD in 1999 for studies on the extracellular proteases in cell invasion and tissue remodeling (supervisors: Profs. Francesco Blasi and Antti Vaheri). For his postdoctoral training (2005-2011), Dr. Teesalu joined the laboratory of Prof. Erkki Ruoslahti at Sanford Burnham Prebys Medical Discovery Institute in La Jolla (USA) to work on identification of tumor homing peptides and characterization of vascular ZIP codes in vascular trees of normal organs. This work led to identification of a new family of homing peptides, tumor penetrating peptides, that upon tumor recruitment extravasate and trigger a cell- and tissue penetration pathway.
Awards and recognitions to Prof. Teesalu include S. Komen for Cure Career development award (2010),- – ERC starting grant (2010), Wellcome Trust senior international fellowship (2010), EMBO installation grant (2010), and Estonian National Prize in Medicine (2017). Tambet Teesalu holds a visiting professorship at the Center of Nanomedicine of University of California Santa Barbara (USA) and visiting associate professorship at Sanford Burnham Prebys Medical Discovery Institute, La Jolla (USA).- On non-academic side, he has founded 3 biotech companies including DrugCendR Inc. (La Jolla, USA) that develops tumor penetrating peptides for solid tumor targeting.