Project

Anti-Cancer Light-Controllable Antibody-Peptide Conjugates

Objectives

Project ALISE integrates the expertise, resources and knowledge of participating Institutions focusing on design, synthesis and preclinical study of conjugates of monoclonal antibodies with peptides whose anti-cancer activity can be enhanced in tumours by irradiation with light (LC-APCs). The second objective of the Project is to develop the design principles for the LC-APCs which would enable their further commercialization as anti-cancer agents and obtain the LC-APCs which would demonstrate favorable pharmacological characteristics and efficacy in vivo on animal models. The application of LC-APCs against one of the deadliest human diseases – locally advanced pancreatic cancer – will be the ultimate goal of the post-Project sustainable collaboration. The third objective of the Project, which is strongly connected to the other two, is sharing the knowledge via staff exchange between the participants, training, as well as dissemination of new knowledge to the public.

Main idea

The idea behind the project consists in combining the primary advantages of both, antibody drug conjugates (ADCs) and light-controllable cytotoxic peptides. LC-APCs will deliver the peptides to the sites of action – the tumor cells – with high level of safety, specifically interacting with tumor-associated antigens, to release the peptide molecules there and then. The control of the peptide cytotoxicity by light will provide a second level of safety to sharply enhance the peptide activity on-site. Switching the cytotoxicity “on” with non-thermal red light irradiation in tumors will allow avoiding side-effects in the healthy tissues. Irradiation will be used to reach places where ADCs underperform, narrowing the cell-killing activity only to solid tumors. In other words, while ADCs may be considered as the “magic bullets”, a concept introduced by Paul Ehrlich, the ability to control the bullet’s action by light can be regarded as the “laser sight” of the weapon.

antibody raised against tumor-specific antigen
linkers cleavable in tumor cells and microenvironment
peptide payload capable of photo-regulated cytotoxic activity

Schematic representation of a light-controllable antibody-peptide conjugate (LC-APC).