Characterization of new Radio Immuno Therapies Auger and Alpha for Cancer treatment. – RITAa

France has a particular and fascinating history in nuclear energy and radiation use for medical purpose, which led our country to develop unique skills and an undeniable technological lead. In the project RITAa, we will explore the therapeutic potential of innovative internal radiotherapy using new radionuclides (produced by Orano) and delivered to tumor by carriers targeting externalized proteins specifically expressed by cancer cells characterized at the Cancer Research Center of Lyon (CRCL).

Indeed, we have recently characterized externalized proteins highly specific of cancer cells, making them prime targets for therapy. Four of them, which are at different stages of characterization in terms of type of pathology, presence of a carrier (antibody, peptide), etc…, were chosen for their biological properties. The ambitious challenge of the project is to address different innovative metals that emit Auger electrons or a-particles to tumoral cells in order to destroy them. The final goal of the project is to find the best combination target/carrier/radiation emitter, in order to characterize one or more radiopharmaceuticals compatible with clinical development in humans at the end of the project. We will thus focus on a-therapy and Auger electron therapies that have been described as better alternatives than ß- therapy, in terms of therapeutic efficacy, damage to healthy tissues, and administration dose. We will design new molecules coupling our carriers (peptides, antibodies) to these different radionuclides to specifically target cancer cells. Different combinations of target/carrier/radionuclides illustrating different mechanisms of action of radionuclides (internalized or not, long/short half-life, dose, energy deposited…), will be investigated. The objective is to explore the accumulation of each selected compound in the tumoral lesions, and to study its anti-tumor activity and safety.

RITAa?achievements.
I) We will establish a unique pipeline connecting an industrial radionuclides provider, academic research teams and heath care center for the development of innovative internal radiotherapeutic solutions.
II) This pipeline will enable us to promote Auger-emitters and a-emitters use in cancer, offering new opportunities to patients without therapeutic solutions.
III) The development of such a strategy will be made possible by carrying out a comprehensive research program, necessary to characterize already identified extracellular targets (in terms of expression in cancerous tissue, secretion, etc...)
IV) At the end of the project, we will deliver a ready to use product to be tested in a Phase I clinical trial directly.
V) This project will globally integrate all the expertise and production means of new radiopharmaceuticals in France as a foundation for a long-term partnership.