Many tumor cells are characterized by the overexpression of certain antigens. Molecules that specifically recognize these structures are suitable as homing devices in tumor therapy. Conjugation of anticancer drugs with such a delivery vector targeting tumors would be a “magic bullet” according to the Nobel laureate Paul Ehrlich. Antibody-drug conjugates (ADC) technology have already been approved for anticancer therapy. However, ADCs have limitations with respect to tumor penetration, high manufacturing costs, and require challenging conjugation chemistry. Peptide-drug conjugates have a high drug loading capacity, easily penetrate tissue, and can be cost efficiently prepared in a homogenous form with straightforward and well-defined conjugation chemistry.
The ETN allows to develop and validate an array of new peptide-drug conjugates combining either known tumor-specific peptides or newly discovered tumor-homing peptides with potent cytotoxic drugs. The tumor-selective peptides are designed for cellular uptake mediated either by endocytosis or by cell-penetrating peptides.
The combination of an array of tumor-selective peptides targeting different receptors and different uptake mechanisms with diverse antitumor drugs acting on different cellular targets is a powerful strategy to minimize potential risks on healthy cells and increase the efficacy toward tumors. Because the number of receptors on tumor cells is limited, the combination of different target peptide–drug conjugates may enhance the bioactivity. The influence of the treatment schedule of such combination therapy on the antitumor activity will also be evaluated.
The consortium of the ETN MAGICBULLET brings together interdisciplinary expert knowledge in tumor biology, drug discovery, biochemistry, pharmacology, cell biology, organic chemistry, peptide chemistry, synthetic chemistry, medicinal chemistry, spectroscopy, conformational analysis, and computational chemistry. The training program focuses on multidisciplinary research to explore and validate molecular targets for innovative treatment or investigations on the molecular mechanisms in organ-specific metastatic growth processes. It aims at scientific multilingualism and relies on concerted learning, a combination of introductory training, hands-on learning “on the bench”, teaching by peers, and training in additional skills. This high complementarity is required for the different scientific tasks in the development pipeline.
The ETN MAGICBULLET is a tool that can: