European Network on Anti-Cancer Immuno-Therapy Improvement by modification of CAR and TCR Interactions and Nanoscale Geometry

Project Information

EN_ACTI2NG

Grant agreement ID: 721358

DOI

10.3030/721358

Project closed

EC signature date 31 August 2016

Start date 1 January 2017

End date 30 April 2021

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 2 539 859,76

EU contribution

€ 2 539 859,76

Coordinated by

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Spain

Periodic Reporting for period 2 - EN_ACTI2NG (European Network on Anti-Cancer Immuno-Therapy Improvement by modification of CAR and TCR Interactions and Nanoscale Geometry)

Reporting period: 2019-01-01 to 2021-04-30

Summary of the context and overall objectives of the project

Cancer is one of the main causes of death within Europe. Given the aging of the population it can be expected that the number of Europeans suffering cancer will increase in the coming years. It is therefore important to develop and optimize anti-cancer therapies. Recently, immunotherapy against cancer, based on using a patient’s own immune system to eradicate cancers, was introduced into the clinic. This approach has provided a qualitative change in the treatment of various cancers, leading to long term survival of patients whose life expectancy with more traditional therapies (radio- and chemotherapy) was much more limited. This therapy is still at its very early stages of development and needs to be optimized to reduce side effects and be expanded to more types of tumors. Europe is lagging as compared to the USA and China in the development of these therapeutic approaches, thereby missing out on important clinical and economic opportunities. The EN-ACTI2NG network (European Network on Anti-Cancer ImmunoTherapy Improvement by Modification of CAR and TCR Interactions and Nanoscale Geometry) trains 10 early stage researchers (ESRs) in the development of immunotherapy approaches centered on genetic modification of the patient’s white blood cells with receptors that can recognize the tumors. Scientific projects are aimed at 1) understanding the molecular mechanisms underlying the function of these receptors, in order to develop more rational ways of designing such receptors, 2) optimizing function by defining new formats and altering interaction modes of these receptors and 3) to isolate receptors recognizing new targets on the tumor cells, thereby expanding the clinical reach of this therapy. Via additional training in research techniques, career planning and communication skills and by performing secondments with research groups and companies that have complementary approaches the early stage researchers should receive a multidisciplinary education that should allow them to embark on a successful professional career in development or implementation of immunotherapy.

The scientific achievements at the end of this project include the development of new formats of cancer-specific immune receptors that have shown improved response to tumors in pre-clinical models of cancer immunotherapy, isolation and characterization of new immune receptors specific for certain types of leukemia, and new tools and findings that help us understand how these cancer-specific immune receptors work. The 10 ESRs have completed their scientific and complementary training program and will prepare and defend their PhD dissertation over the course of the next two years, providing them with a solid education and preparedness to further academic, industrial or regulatory careers in cancer immunotherapy or related research areas. As a matter of fact, the first ESR to graduate this spring will join a recently founded cancer immunotherapy company to head a R&D laboratory on CAR-T cell development.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The outcome of the research performed under the EN-ACTI2NG program includes the development of new techniques and devices that allow very detailed and efficient analysis of the mechanisms underlying tumor-specific antigen receptor signaling, generation of new tumor-specific receptors that will be tested in the clinic and various approaches that improve cellular anti-tumor therapy: generation of immune cells that rely on the activity of two different receptors to attack the tumor, thereby enhancing the specificity of these cells for tumor cells; co-receptors that can enhance the usually weak anti-tumor responses of immune cells; inclusion of new signaling domains in tumor-specific recombinant receptors that have shown promise in preclinical models of cancer immunotherapy; and a completely new class of RNA based co-stimulators that can enhance weak immune cell responses and that have been successfully tested in pre-clinical models of infection and anti-tumor responses.

Ten articles describing this research have been published in peer-reviewed journals at the closing date of this project and more manuscripts are under review or are being prepared for submission. Three patent applications have been filed and licensing agreements have been reached that should facilitate the further development of these findings into applications that improve treatment and outcome for patients. Findings of the EN-ACTI2NG network and other groups in the field of cancer immunology have been shared via Twitter (@enacti2ng) and Facebook (The EN-ACTI2NG Initial Training Network), students have shared their experience as young researchers via blogs and podcasts and interviews (see http://www.enacti2ng-itn.eu/ and our social media channels) and an animation video explaining cellular cancer immunotherapy and the role of the EN-ACTI2NG network in the development of this important clinical approach has been made (https://www.youtube.com/watch?v=zo8LCn79QQc).

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The actions developed under the EN-ACTI2NG project have provided various unique approaches to improving the cellular antitumor response, not only working on new designs of current tumor-specific immune receptors but also introducing completely new ways of boosting these responses with additional receptors and pharmacological agents. The already established procedures and infrastructure to move cancer-specific immune receptors to clinical trials and the clinic allow that these improvements and innovations could make it to their therapeutic application within a relatively short time frame. The licensing of a patent on a new leukemia-specific receptor isolated during the course of this action is a clear example of the relevance of our findings and the socio-economic impact it will likely have. Finally, EN-ACTI2NG educated a group of smart, ambitious and enthusiastic researchers coming from 10 different countries with knowledge and skills that can in their further career strongly contribute to the development and implementation of new clinical approaches to cancer in academia, clinics and companies in Europe and the world.

esr-pi-webs-reducida.jpg