Preclinical characterization of new targeted lytic peptides
Cell-penetrating peptides provide a unique platform to create a new generation of cancer therapeutics with enhanced efficacy and diminished toxicity. Using phage display technology, we have selected several cancer cell-binding peptides and antibodies. The conjugation of such cancer cell-specific binders to cationic peptides, known as lytic peptides, led to the design of conjugates that killed cancer cells but not normal cells in vitro. Moreover, we have developed a lytic fusion peptide that killed M2 macrophages. M2 macrophages are characterized by their involvement in tissue remodeling and tumor promotion. In the proposed project, we aim to test the anti-tumor activity of a lytic peptide D(KLAKLAK)2 linked to a cancer homing peptide or an antibody.
Despite new cancer treatments, the emergence of resistance during immunotherapy or chemotherapy is a significant challenge that must be addressed. Thus, novel targeted strategies are urgently needed. The present project aims to develop new targeted lytic peptides to specifically kill cancer cells and spare normal cells. Notably, an effective treatment should have a beneficial effect on the distress level of patients and their family members. Moreover, an improved targeted therapy allows better treatment response and potentially reduces complication related to drug toxicity of chemotherapy thereby reducing morbidity and the cost of prolonged hospitalization. With respect to education, master and PhD theses are expected to emerge from the development of the present project.
In these experiments two mouse strains will be used: Athymic Nude - Foxn1nu 192 mice and C57BL/J6 120 mice.
During experimental procedures animals will not experience any significant pain or distress nor impairment of general condition.
Animal experiments are the only useful model to test the hypothesis and the suggested number of animals is minimal requirement to obtain reliable data.
We have tried our best to refine the animal experimental protocols in terms of pain management and endpoints.
Despite new cancer treatments, the emergence of resistance during immunotherapy or chemotherapy is a significant challenge that must be addressed. Thus, novel targeted strategies are urgently needed. The present project aims to develop new targeted lytic peptides to specifically kill cancer cells and spare normal cells. Notably, an effective treatment should have a beneficial effect on the distress level of patients and their family members. Moreover, an improved targeted therapy allows better treatment response and potentially reduces complication related to drug toxicity of chemotherapy thereby reducing morbidity and the cost of prolonged hospitalization. With respect to education, master and PhD theses are expected to emerge from the development of the present project.
In these experiments two mouse strains will be used: Athymic Nude - Foxn1nu 192 mice and C57BL/J6 120 mice.
During experimental procedures animals will not experience any significant pain or distress nor impairment of general condition.
Animal experiments are the only useful model to test the hypothesis and the suggested number of animals is minimal requirement to obtain reliable data.
We have tried our best to refine the animal experimental protocols in terms of pain management and endpoints.