A new, very promising combination of treatments
On February 4, 2017, Institut Curie and the company Onxeo, announced the launch of a series of studies on the usefulness of combining radiotherapy with immunotherapy and DNA repair inhibitors. This represents real hope for patients suffering from cancer that resists standard treatments.
Immunotherapy is indisputably a new and valuable weapon in the fight against cancer. However, despite the impressive results against certain tumors, 80% of patients do not respond to these new therapeutic strategies. “Generally speaking, these patients are suffering from a cancer whose DNA is not highly mutated and does not produce neoepitopes,” explains Sebastian Amigorena, director of the Immunotherapy center for cancer at Institut Curie. “These small molecules characteristic of these cancers carry a mutation of a specific gene of the tumor cell, and act as a red flag to trigger the immune system to act on dangerous cells.”
The lack of effectiveness of some immunotherapies seems to be linked to the presence of DNA alterations and, very certainly to the existence of an ability, even a residual one, to repair lesions. Marie Dutreix, research director at Institut Curie (Orsay site), is a renowned specialist in DNA repair mechanisms and spearheaded a new very promising class of products: Dbaits, agents that accentuate the effects of treatments such as radiotherapy.
The combination of radiotherapy and Dbait has already shown very promising results in humans. The DRIM test (1), performed in patients suffering from melanoma with dermal metastases, showed good tolerance of AsiDNA™ (the clinical form of Dbait, acquired in 2016 by Onxeo) administrated locally, and gave complete response rates 4 times higher than those observed with radiotherapy alone. Clinical trials combining radiotherapy and immunotherapy have already proven the effectiveness of this combination. The triple combination may help to reach a new stage in the fight against cancer.
A virtuous circle against cancer
In concrete terms, this combination with immunotherapy would work like a virtuous circle, with each therapeutic approach contributing to the effectiveness of the others:
- radiation by radiotherapy leads to the death of the tumor cells, which stimulates the expression of inflammation genes and thus the immune system
- AsiDNA aims to amplify the effect of radiation by preventing the repair of damage created by the radiation on the tumor’s DNA It thus increases the effectiveness of radiotherapy and the “immunogenic death of tumor cells”
- immunotherapy increases the immune system’s ability to recognize tumor cells and destroy them
This project is particularly important to the specialists at Institut Curie, who are seeking to develop Marie Curie’s most valuable legacy: radiotherapy. Onxeo, specialized in research and development in new treatments for orphan cancers, is also excited about “this new program that adds to the ambitious development plan already in place and strengthens our work with Institut Curie,” states Judith Greciet, General manager of Onxeo.
To accelerate development and research in radiotherapy, Institut Curie will welcome a new recruit in March: Professor Philip Poortmans. Currently head of the radio-oncology department at Radboud university medical center in Nijmegen in the Netherlands, and professor at Radboud university, he will take over as head of the radiotherapy department at Institut Curie in March 2017. He will provide his preclinical and clinical expertise on this project that aims to validate this new therapeutic approach for patients. “The combination of AsiDNA with radiotherapy and immunotherapy could be a revolutionary innovation with a high potential for development,” he explains hopefully.
Professor Poortmans joins Institut Curie
To accelerate development and research in radiotherapy, Institut Curie will welcome a new recruit in March: Professor Philip Poortmans. Currently head of the radio-oncology department at Radboud university medical center in Nijmegen in the Netherlands, and professor at Radboud university, he will take over as head of the radiotherapy department at Institut Curie in March 2017. He will provide his preclinical and clinical expertise on this project that aims to validate this new therapeutic approach for patients. “The combination of AsiDNA with radiotherapy and immunotherapy could be a revolutionary innovation with a high potential for development", he explains hopefully.
